View
214
Download
1
Category
Tags:
Preview:
Citation preview
So many seizures…so many drugs…
What to choose and when
Courtenay Freeman, DVM, DACVIM (Neurology)
Southeast Veterinary NeurologyQuickTime™ and a decompressor
are needed to see this picture.
Objectives
• Description
• Lesion localization
• Work up
• Management
Definitions
• Seizure– The clinical manifestation of an abnormal
and excessive synchronization of a population of cortical neurons
• Epilepsy– Tendency toward recurrent seizures
• Unprovoked by systemic or acute neurologic insults
Definitions• Prodrome
– Longterm indication of seizure– hours to days before seizures
• Aura– Initial sensation of seizure before observable
signs– seconds-minutes prior to seizure
• Ictus– Seizure itself, usually 1-3minutes
• Post ictus– Transient abnormalities in brain function– Several hours to 1-2 days, 3-4 days (horses)
Classification
focal generalized
Impairment of consciousness
No impairment of consciousness
seizure
Secondarily generalizes
Absence
Tonic-clonic
Myoclonic
Tonic/clonic/atonic
QuickTime™ and aYUV420 codec decompressor
are needed to see this picture.
Classification
Seizure
Intracranial Extracranial
Structural
Functional
Metabolic Toxic
•Vascular•Infect/infl•Trauma•Anomaly•Neoplasia•Cryptogenic
•Inherited/Idiopathic
Differentials
• Syncope
• Narcolepsy/Cataplexy
• Vestibular episodes
• Movement disorders
QuickTime™ and aMotion JPEG OpenDML decompressor
are needed to see this picture.
Narcolepsy
QuickTime™ and aMotion JPEG OpenDML decompressor
are needed to see this picture.
Idiopathic head bobbing
QuickTime™ and ah264 decompressor
are needed to see this picture.
Lesion Localization
• Forebrain or Prosencephalon– Rostral to tentorium
cerebelli
• Includes• Cerebrum (telencephalon)• Thalamus (diencephalon)
Forebrain dysfunction
• Altered mental status and behavior changes
Gait and Posture
• Normal gait– Pleurothotonus • body turn toward lesion
– Circling (toward)
• Postural reactions– Deficits on contralateral side
Menace response
• Absent contralateral to lesion• Normal PLR
Sensory
• Facial hypoalgesia• Hypoaesthesia on
contralateral side of body
• Hemineglect– Ignore sensory
input from one half of their body• Eat out of one half
of bowl
QuickTime™ and a decompressor
are needed to see this picture.
OtherSeizures!!
QuickTime™ and aMotion JPEG OpenDML decompressor
are needed to see this picture.
Idiopathic epilepsy
• Recurrent seizures with no identifiable cause
• Genetic predisposition• Cryptogenic epilepsy– No identifiable cause– No genetic predisposition
QuickTime™ and a decompressor
are needed to see this picture.
IE: Signalment
• 6 months to 6 years of age• Normal neurologic examination• Normal inter-ictal examination• Purebred dog
QuickTime™ and a decompressor
are needed to see this picture.
QuickTime™ and a decompressor
are needed to see this picture.
Diagnostics
• Minimum data base– CBC– Chemistry Profile– Urinalysis–+/- Liver function tests
• Advanced imaging??
Who should be imaged?
• Asymmetrical neurologic examination• Abnormal inter-ictal period• Patients > 6 years old
• All dogs??
Treatment
• Goals?– Maintain seizure control– Limit unacceptable side
effects– Seizure control ≠ elimination
• When to start?
Seizure therapy
PRINCIPLES
• Life-long daily treatment
• Frequent reevaluations are necessary
• Potentials for emergency situations
• Inherent risks of the drugs
Seizure therapy
When to start?
• Intracranial disease • Status epilepticus• Cluster seizures• 2 or > isolated
events in 4 - 6 wk period
Phenobarbital
– “Broad spectrum”
– Increases seizure threshold
– Decreases spread of seizures
– Good first line drug• Controls ~ 80% of IE dogs
Phenobarbital
Dose (a) Dog - 2 - 4 mg/kg every 12 hours
(b) Cat – 1.5 - 2.5 mg/kg every 12 hours
Therapeutic serum concentration (a) Dog - 15 - 40 µg / ml
(b) Cats - 23.2 - 30.2 µg / ml
How to use PB ?
5.5 time T1/2 = 10 to 14 days
Dosing interval << T1/2 (accumulation)
15
45
2-4 mg/kg twice daily
Phenobarbital
– T1/2; Steady State (SS)• Dog – 32-90 hours; 10-18 days• Cat – 34-43 hours; 10-14 days• Horse – 14-25 hours; 3-6 days
– 90-100% Bioavailable
– Peak conc. 4-8hrs
– Primarily Hepatic metabolism• Up to 25% excreted unchanged by
kidneys
Loading Dose
Total Phenobarbital loading dose: 18 to 24 mg/kg intravenously over 24 hr
Loading 10 to 14 days
Phenobarbital: adverse effects
Idiosyncratic
(1) Hyperexcitability
(2) Acute toxic hepatopathy in dogs
(3) Immune-mediated bone marrow suppression
(4) Lymphadenopathy in cats (pseudolymphoma)
(5) Superficial necrotizing dermatitis
(6) Facial pruritus and limb edema (cat)
QuickTime™ and a decompressor
are needed to see this picture.
Phenobarbital: adverse effects
Dose-related / transient
(1) Sedation (2) Polydipsia & polyuria (3) Polyphagia
(less common in cats) (4) Pelvic limb weakness
Phenobarbital: adverse effects
Laboratory changes
(1) Elevation of serum ALP (2) Depression of serum albumin
(3) Serum T4 and fT4 significantly depressed in 60-70% dogs (minimal fluctuation in TT3)(4) Serum TSH may even be elevated in <7% dogs (slow, compensatory)
(5) Cholesterol high normal
QuickTime™ and a decompressor
are needed to see this picture.
Potassium Bromide
• No biotransformation• Competes with Cl-
• Hyperpolarization• Synergistic effects• Controls 80% of refractory
cases• Entirely excreted by kidneys
Potassium Bromide
• 30 mg/kg/day orally • T1/2 (dog): 25 to 46 days (cat 10 days)• Steady state (dog): 3 to 6 months• Serum concentration: 800-1500 µg/mL
Potassium Bromide
Loading dose :Total dose = 600 mg/kgDivided over 4 days = 150 mg/kg/day
Risks = vomiting / extreme sedation
Potassium Bromide
• PuPd, Polyphagia, • Pruritus• Hyperactivity/ behavioral
change• Pancreatitis (with PB)?• Asthma in cats– Allergic Pneumonitis 35-42%– Idiosyncratic– Resolves over 1-2 months
Bromism
• Dose-dependant• Ataxia, Sedation • Pelvic limb stiffness and weakness
Benzodiazepines
• Mechanism of Action– Increase the
frequency of the chloride channel opening
– Hyperpolarizes cell
Diazepam
• Half-life: – Dogs ~ 3hrs – Cat ~ 8-10hrs
• Develop tolerance to medication• Rapid withdrawal may induce
seizures
Diazepam
• Emergency management of seizures
• Limited use in dogs
• 0.5-1 mg/kg divided bid - tid
• Steady state in 3.5 - 4.5 days
• Monitor liver enzymes after 5 days due to risk of hepatic necrosis
Adjunctive MedicationClorazepate
• Metabolized to nordiazepam
• Tolerance develops but slower than to diazepam
• 0.5 mg/kg q8-12 hrs
• Useful for ‘breakthroughs’ as only effective for 2 months
Gabapentin / PREGABALIN
• Structural analogue of GABA
• Binds to the a2-d sub-unit of high voltage pre-synaptic calcium channels– Decreases NT release
• Half-life 3-4 hrs
• 30% metabolized in liver – rest unchanged in urine
Gabapentin (Neurontin)
• Metabolized in liver
• T1/2 3-4 hrs
• 10-20 mg/kg TID PO
• 50% improved control
• Do not use liquid formulation!
Levetiracetam
• Binds to a synaptic vesicle (SVA2)– Modulates of neurotransmitter release,
reuptake, recycling
• Half-Life 2-4 hrs
• Excreted primarily through kidney
• HONEYMOON EFFECT– Dogs develop recurrence of seizure
frequency – tolerance?
Levetiracetam
• 20 mg/kg tid PO (Keppra XR?)
• Use higher dose when with PB
• 50% improved control
• IV use in emergencies
• Ataxia & sedation
Zonisamide
• Synthetic sulfonamide
• “Broad spectrum”/multi-modal
• Half-life 17 hrs (dog), ~35 hrs (cat)
• Liver metabolism
Zonisamide (Zonegran)
• 50% refractory epileptics respond
• 5-10 mg/kg bid PO
• Need increased dose with PB
• Side Effects– Transient sedation, ataxia– Acute hepatoxicity (idiosyncratic)– KCS
Felbamate• Mechanism of action– Inhibits NMDA and kainate receptor
activation– Inhibits voltage dependent Na+ channels
• High bioavailability• T ½ of 4-6 hours• 70% excreted in urine unchanged, 30% liver
• Side Effects– blood dyscrasias, hepatotoxicity
Status epilepticus
• Definition: seizure activity > 5 min• Cluster seizures: 2 or > seizures in a 12
to 24 hour period
• Anticonvulsants: drug to stop seizure activity
• Antiepileptic: drug to prevent seizure activity
Status epilepticusADMISSION MANAGEMENT
• History• Rectal temperature – cool if >104˚F/40˚C• Blood work – Electrolytes/ Ca++ / Glucose / bile acids /
Toxicity screen / PCV / TP• +/- Dextrose 10% solution; 100 mg/kg IV• Oxygen administration• +/- IV catheter
Status epilepticusTreatment #1
• Stop seizure activity1. Diazepam– 0.5 - 1.0 mg/kg IV, 0.5 - 2.0 mg/kg rectally or IN– Midazolam 0.2 mg/kg IV/IM/nasally
2. Phenobarbital 2-4 mg/kg IV/IM– Onset of action ~20 min– q 30 min intervals if needed (20-24 mg/kg/24 hr)
Status epilepticusTreatment #2
• Valium/midazolam CRI– 0.5 - 2.0 mg/kg/hour IV CRI in 0.9%
saline– Respiratory depression possible– Reduce dose q3-6 hr to effect
Status epilepticusTreatment #3
• Levetiracetam (Keppra) IV
• Anticonvulsant and anti-epileptic
• 20 to 60 mg/kg IV over 2 minutes lasts 8 hours (dilute)
Status epilepticusTreatment #4
• Barbituate coma– Pentobarbital 3 - 24 mg/kg
IV to effect– Profound respiratory and
cardiac depression– Especially if toxin induced
seizures
• Propofol coma– Anticonvulsant properties– Bolus 1-4 mg/kg IV to
effect – CRI (0.1-0.6 mg/kg/min)– Consider expense
Status epilepticusTreatment #5
Last Ditch!!• Inhalational Anesthesia vs.
thiopental
• Ketamine – 5mg/kg IV then 5 mg/kg/hr
• Potassium bromide rectally – 100 mg/kg q4hrs 6 doses
Status epilepticusTreatment #6
• Cerebral edema?– Oxygen and Fluids– Methylprednisolone sodium
succinate?– Furosemide 1.0 mg/kg IM, IV– Mannitol 20% 0.5 g/kg IV
Status epileptusPost seizure management
• Thoracic and Abdominal imaging• Urinalysis / Indwelling urinary catheter• ECG• CT / MRI• CSF• +/-Gastric lavage
Questions?QuickTime™ and a decompressor
are needed to see this picture.
Courtenay Freeman, DVM, DACVIM (Neurology)
Recommended