BRAIN - Epilepsy Flashcards
mutation/mode of inherence/breed associated with juvenile myoclonic epilepsy
Rhodesian Ridgeback
mutation DIRAS1 (role in acetylcholine release and neurodevt)
fully penetrant autosomal recessive
clinical signs associated with juvenile myoclonic epilepsy
myoclonic seizures occuring mainly during relaxation
generalised tonico-clonic seizure in 1/3 of patients
35% photosensitive
absent seizure
2 antiepileptic treatements in juvenile myoclonic epilepsy
levetiracetam
potassium bromide
in human valproic acid
EEG in juvenile myoclonic epilepsy
ictal and inter-ictal
generalised and irregular 4-5 Hz spike and wave complexes and polyspike-waves complexes
with a fronto-central maximum
Which gene is associated with epilepsy in Lagotto Romagnolo and Belgian Shepherd?
Lagotto Romagnolo: LGI2
Belgian Shepherd: ADAM23
DDx episodic disorders
Syncope
Narcolepsy
Cataplexy
Seizure
Neuromuscular weakness
Paroxysmal behaviour changes (compulsive disorders)
Vestibular attack
Idiopathic head tremor
Paroxysmal dyskinesia
SNC-SNP-VIP
How many dogs with frontal lobe neoplasia are presented with seizure as the first clinical sign?
75%
What are the prediction factors of early seizure recurrence in dogs acording to epilepsy type?
Epileptic seizures recurred in 50% of patients within a mean time of 7 hours.
IE: abnormal postictal neurological examination with prosencephalon signs
Structural epilepsy: one seizure 72 hours before hospital admission and abnormal neurologic examination
Reactive seizures: long-term antiepileptic monotheraphy
All dogs: abnormal neurological examination, occurrence of cluster seizures, status epilepticus, or combination of them 72 hours before presentation
What breed of cat is associated with audiogenic reflex seizures? And what kind of seizures?
Birman
Myoclonic seizures, frequently occurring prior to GTCS
late onset (median 15 years) and absence seizures (6%), with most seizures triggered by high-frequency sounds amid occasional spontaneous seizures (up to 20%).
Which EEG rhythm is associated with REM-sleep?
Beta (higher than 12.1 Hz)
What are the factors significantly associated with short term mortality in SE.
Increased patient age
Shorter duration of hospitalization
Development of SE before arrival
SE caused by a potentially fatal etiology
Audiogenic reflex seizures are usually associated with deafness or hearing impairment: true or false?
True
Half of the population
What are the two most common causes of reactive seizures in dogs?
Intoxication & hypoglycemia
What are clinical features associated with DIRAS1 epilepsy?
Juvenile onset
Absence seizures
Myoclonic seizures with propagation to generalized tonic-clonic seizures (38%)
Photosensitivity (35% observed, 66% in EEG)
Nodding of the head
4-5Hz spike-and-wave complexes and polyspike-wave complexes with a fronto-central maximum
Which test is useful for differentiating seizure and syncope? Is this test specific and/or sensitive? What does it mean (confirmation, exclusion…)?
ROC analysis of sPi as a marker of GTCS yielded an AUC, with an optimum cutoff point of 0.97 mmol/L, corresponding to specificity and sensitivity levels of 100% and 44%.
Hypophosphatemia only in seizure group. Especially with sPi < 0.97 mmol/L, may be useful in clinical practice to rule in GTCS.
Give 5 genetic epileptic conditions.
Idiopathic: Belgian Shepherd (ADAM23, RAPGEF5), Dutch partridge dog (CCDC85A)
Juvenile benign: Lagotto Romagnolo (LIG2)
Juvenile myoclonic epilepsy with photosensitivity: Rhodesian Ridgeback (DIRAS1)
Severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration: Parson Russell Terrier (PITRM1)
Myoclonic epilepsy with neuronal glycoproteinosis (Lafora): Beagle, Chihuahua, French Bulldog, Griffon Bruxellois, Miniature Wirehaired Dachshund, Newfoundland, Pembroke Welsh Corgi, Domestic Shorthair (NHLRC1 = EPM2B)
At which age the EEG characteristics stabilize?
The characteristics of the EEG corresponding to the adult animal begin to appear at 12 months of age but stabilize after 24 months of age.
Intranasal midazolam has the same efficiency in status epilepticus management than intrarectal midazolam: true or false?
False
IN-MDZ is superior to IR-MDZ: IN-MDZ and R-DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively. All dogs showed sedation and ataxia.
Which AED is associated with the more highest prevalence of adverse effect? Give the %
A significant relationship was identified between the occurrence of reported AEs and monotherapy group, with a higher prevalence in the PB group (77%) and a lower prevalence in the ZNS group (39%).
What is the autoimmune syndrome associated with phenobarbital in dog? What serology can be tested?
Systemic lupus erythematosus
Anti-nuclear antibody (ANA)
What is the most frequent cause of status epilepticus as first epileptic manifestation in dogs?
Structural: 45%
Reactive: 31%
Idiopathic: 23%
mechanism for:
1/ Gabapentine/pregabaline
2/ Phenobarbital
3/ Zonisamide
4/ Potassium bromide
5/ Levetiracetam
6/ Imepitoin
1/ Binds to α2δ subunit of VGCa channel
2/ Activate GABAa receptor directly and indirectly by allosteric action (alpha-beta)
3/ Inactivate Na+ channel, increase GABA release and modulate VGCa channel type T
4/ Hyperpolarise neurons by passing through the neuronal chloride channels
5/ Binds synaptic vesicle protein SV2A, modulates neurotransmiter release
6/ Activate GABAa receptor via BZP (beta-gamma) site with low affinity (partial agonist)
What are the findings predictors of postictal changes?
Which brain sites are commonly affected?
Predictors of postictal changes:
- Epilepsy of unknown origin
- Cluster seizures or status epilepticus
- Lower time from last seizure to MRI
Brain sites
- Piriform lobe
- Hippocampus
- Temporal neocortex
- Cingulate gyrus
molecule for myoclonic seizures
levetiracetam
Definition of an epileptic seizure
Manifestation of excessive synchronous, usually self-limiting epileptic activity of neurons in the brain, resulting in transient occurrence of signs which may be characterized by short episodes with convulsions or focal features
Potassium bromide treatment was strongly associated with high hair arsenic in dogs with idiopathic epilepsy: true or false?
True
Levetiracetam is an interesting AED which is best used as an add-on in a pulse administration protocol because
1. Long term Levetiracetam increases other AEDS side effects
2. Levetiracetam has a high long term toxicity
3. Some dogs develop progressive tolerance to the treament in the case of prolonged treatment with Levetiracetam
4. Long term maintenance, as an add-on AED decreases other AED serum concentration, especially PB
3
ABCB1 gene mutation is associated with refractory idiopathic epilepsy in Australian Shepherd: true or false?
False
Only in Border Collies
Give 3 molecules that can increase serum concentration of phenobarbital and the associated mechanism.
Antiacids: cimetidine, omeprazole, lansoprazole
Antibiotics: chloramphenicol, trimethoprim, fluoroquinolones, tetracyclines
Antifungal: ketoconazole, fluconazole, itraconazole
Others: fluoxetine, felbamate, topiramate
Inhibition of hepatic microsomal cytochrome P450 enzymes
prevalence epilepsy dog
0.6-0.75%
most common seizure type in dog
focal epileptic seizure evolving into generalised epileptic seizure
definition epilepsy
disease of the brain characterized by en enduring predisposition to generate epileptic seizures. Usually practically applied when 2 ore more unprovoked epileptic seiz at least 24h apart
criteria for genetic epilepsy
genetic testing
breed prevalence > 2%
genealogical analysis or familial accumulation of epil individual
EEG % interictal paroxysmal episod in dog with IE
25%
toxic causing epilepsy
carbamate, organoph, lead, etylene glycol, metaldehyde, strichnine
% dogs with reactive seizure presented in status + higher risk ?
41%
higher risk
% dogs with structural epil which have a normal neuro exam
epilepsy first sign in … of dogs with intracranial disease
more frequent local for structural brain disease assoc with seiz
23%
76%
frontal lobe
focal seizure are more frequent in structural epil T/F
false, 20% in both cases
time for disparition of post ictal MRI change
+ histological changes
10-16 weeks
oedema, neovascularisation, reactive astriocytosis, acute neuronal necrosis
- tier 1 confidence level of idiopathic epilepsy
- tier 2
- tier 3
- > 2 unprovoqued epil >24h apart
6m-6y
unremarkable interictal physical exam (except EAD-induced an post-ictal)
blood test (CBC, biochemistry profile, electrolytes, cholest, TG, bilirubin, fasting bil ac and/or amonic)
urinalysis - fasting and post prand bile acide, MRI, CSF analysis
- ictal or inter ictal EEG abnomalities
post ictal change CSF
mild pleocytosis (up to 12/uL) when < 12h
association between CSF WBC count and interval since last seizure
no assoc prot, cluster seizures
link age, interict period and cause of epil
Structural more fqt <1y and >7y
IE more probable 1-5y, interictal period>4w
when perform an MRI in dog with epilepsy
age <6m or >6y
interictaly neurological abnomality
status or cluster
drug resistance with a single AED
when is recomanded epilepsy treatment
interictal period <6m
status or cluster
post-ictal signs severe or last longer than 24h
ferquency or duration increasing or seizure severity deteriorating over 3 interictal period
toxic AE in dogs
lamotrigine (cardiotox)
vigabatrin (neurotox + haemolytic)
phenobarbital:
1. efficacity
2. elimination half life
3. peak serum concent
4. plasma binding prot
5. % excreted unchanged in urine
- 60-93%, superior to KBr
- 37-73h (decrease progressively, stabilizes 30-45d)
- 4-8h
- 45%
- 25%
raison for hepatotoxicity in phenobarb
induction cyt P 450 =>increase heaptic production reactive oxygen species
pharmacocinet interaction PHBR
metabolized by cyt P450 or linked to prot
decrease efficacy of levet, zonisamide, benzodiazepine + corticosteroids, cyclosporine, metronidazole, voriconazole, digoxine, digitoxin, phenylbutazone, thiopental
PB metabolism can be inhibited by P450 inhib:
cimetidine, omeprazole, lanzoprazole, chloramphenicol, trimetoprim, fluoroquin, tetracyclines, keto/fluco/itroconazole, fluoxetine, felbamate, topiramate
type 1/2 adverse effect pheno
type 1: sedation, ataxia, polyphagia, PUPD
type 2: hepatotoxicity, anemia, thrombocytopenia, neutropenia, superficial necrolytic dermatitis, pancreatitis, dyskinesia, anxiety, hypoalbuminemia
imepitoin
1. elimination
2. receptor
3. adverse effect
4. dose
- extensively metabolised in liver, ecreted via fecal route
- low afinity partial agonist for GABA A receptor
- polyphagia, hyperact, somnolence, PD, hypersaliv, emesis, diarrhea, prolapse nict mb, decrease vision, sensib to sound
- 10-30 mg/kg BID
KBr
1. elimination half life
2. bound to plasma prot
3. elimination
4. drug interaction
5. adverse effect type 1
6. adverse effect type 2
7. dose
- 25-46 days
- unbound
- unchanged in urine, tubular reabsorption in compet with chloride (high chloride increase elim)
- loop diuretic (furosemide) increase elim
- sedation, ataxia, PL weakness, PUPD, polyphagia, GI irritation
- personality change, persistant cough, increase risk pancreatitis and megaoeso
- bitherap 15 mg/kg BID (loading 625 mg/kg over 48h)
levetiracetam
1. elimination half life
2. receptor
3. adverse effect
4. interaction
5. prot binding
6. elim
- 3-6h
- presynaptic prot SVA2
- sedation, ataxia, vomiting, decrease appetite
- P450 alter disposition: increase dosage with pheno
- minimal
- minim hepat metab, mainly unchanged in urines
felbamate:
1. adverse effect
2. mechanism
3. interaction
4. elimination + half life
- keratocongonctivitis, blood dyscrasia
- inhib glycine-enhanced NMDA-induced intracel Ca current, blokade voltage gated Na channel, inhib voltage gated Ca current
- raised pheno level in a dose dpd manner, elimi reduced with gabapentine
- half life 6h, mainly metab liver
zonisamide:
1. adverse effect
2. mechanism
3. elim half life
4. prot binding
5. elim
6. dose
7. dosage can be altered by
- sedation, ataxia, loss apetite, type 2: hepatox, renal tub acidosis,
neutropenia, erythema multifome - blockage Ca chan, enhancemt GABA release, inhib glutamate release, inhib voltage gated Na channel
- 15h
- low
- hepat metab P450, excretion kidney
- 3-7 mg/kg BID (7-10 with pheno)
- hemolysis
topiramate:
1. mechanism
2. elim half life
3. elimination
- enhance GABA-ergic activity, inhib voltage gated Na and Ca channel, kainate evoked current and carbonic ahnydrase isoenzyme
- 2-4h
- 70-80% unchanged in urine, biliary excretion
def non convulsive EEG seiz/status + prevalence + risk factor
epileptiform discharge lasting at least 10 sec or any pattern with definite evolution in frequency, location or morphology without prominent motor activity
status >10 min
prevalence 29% and 16%
mortality higher than patient without EEG seizures
risk factor ES/ESE: young age, seizure <8h before, history cluster
zonisamide: adverse effect + half life in cat
sedation 17%, ataxia 11%, hyporexia 17%, emesis 5%
non regenerative anemia, metabolic acidosis, increase ALT/ALP, anticonv hypersensitivy syndrome
adv effect with q12h>q24h
half life 30h, steady state 1 w
A median decrease of 1 seizure per month, and 1 (2 for IE) seizure days per month was found across all cats
behavioural comorbidity of epilepsy
attention deficit hyperactivity disorder like
cognitive impairement
fear and anxiety
most prevalent breed with vestibular epilepsy, EEG, prognosis
Pugs
EEG: interictal spikes in fronto-temporal ans fronto-parietal area
100% response to AE
presumed idiopathic cause
effect zonisamide treatment on Phbr concentration
increased (5/9) hepatotoxic dose
metabolised by CYP450
region assoc with seizures triggered by eating
breed overrepresentated
main type of seizures
perisylvian region (maj temporal in hum)
Retrievers
focal evolving in generalised
maj idiopath epil
risk factor for early recurrencence in dogs hospitalized for seizure eval according for StE/IE/RE
IE: abnormal neurol exam
StE: abnormal neurol exam, seizure 72h before
RE: long term
diffusion in dog with epil
increase ADC in amygdala and in semioval centrum (cell loss and increase intercellular space=
risk factor structural epil in cat
pedigree cat, >7y, abnormal neurologic exam, ictal vocal (salivation decrease likelihood)
EEG abnomalies associated with PSS shunts/ intracran pathology/ IE
high voltage low frequency background activity in PSSS and intracran path
bilateral symmetric triphasic: PSS
IE: spike-waves
EEG artifacts
eyes movement: frontopolar elect +/- frontal. Mono, biphasic sharp waveform or complex polyphasic slow waveform (1Hz)
eye blinks: positive pole (cornea) move closer to frontopolar elect: symmetric downward deflexion
EMG: sudden arrytmic burst, prolonged duration and frequency (20-100 Hz)
ECG: electrical (QRS) and mechanical (vessel). Rythmic, regular, temporaly correlated with heart contraction
ear: similar than ocular mobility
Alternating current (50-60 Hz): very high freq, long duration. Serie of sharp, rapid, positive-negative deflection in one or more elect
electrode artifact: brief transient limited to one elect teh low freq high amp rythm across the entire scalp
salt bridge: when 2 elect are too close. unipol mont appear superimposable, isoelect wave in longit montage
preval diagnosis with CSF in normal MRI
0.5%
negative prognostic indicator for status
GME, absence control 6h after hospit onset, partial SE
mortality 25%
phenobarb induced hematol change in cat
75% cytopenia
most freq neutropenia 50%, thrombocytopenia 25% and anemia 20%
even when phbr in therapeutic range, life-threatening 1.5%
interaction canabidiol and pheno
no interaction
histological lesion in cat with familial spontaneous epil
+ perfusion on MRI
lower number of neuron in cornu amnionis 3 hippocampus
hypoperfusion (but other etude with some hyper)
age-realted changes in MRI spectroscopy
young dog increased choline decreased NAA
feline audiogenic reflex seizure
type seizure
age, breed
treatment
prognosis
non progressive, myoclonic (generalised TC when repetitive stimultation) seizures triggered by loud, sudden sound
cat>15yo
Birman
levetiracetam 50% freedom from seiz
higher probability of MRI post ictal change
cluster or status
unknown-origin epilepsy
lower time from last seiz
adverse effect topiramate in cat
renal tubular acidosis
diffusion in epilepstic dog
lower cerebral flow, greather mean time of contrast arival
effect food with adimistration of levet
food slow absorption, decrease plasma concent
diffusion MRI in idiopath epil
interictal DWI: increase dif in piriform
ADC : reduction 3-6h, increase 12-24h, normalisation 48h
DTI: change in cingulate gyrus (lower FA)
spectroscopy in epileptic dog
higher NAA/cho in temporal lobe
reduced NAA/Cr , reduces Glx/cr in thalamus in dogs under treatment
serum marker for structural epilepsy
neurofilament light chain higher than IE
mechanism BBB dysfunction in epilepsy
leakage serum albumine
->binding TGF B in astrocytes
-> reactive astroglyosis
->generation excit synapse, dim GABA inhib, change extracellular matrix
BBB dysfunction in epil dog
higher blood brain barrier permeability in IE
increase activity/expression MMP9 in serum/CSF,
lower gene expression Kir4 (astro K channel) and claudin 5 (endothelial TJ) in pirif lobe
% response of zonisamide for IE dog
76% 50% reduction
55% seizure freedom
adverse effect (13%): reduced appetite, vomit, hindlimb weakness, constip
blokage volt gated Na channel + voltage gated type T calcium channel, enhance GABAA recept function, inhib glutamate release, scavenge free radic
interaction pheno / levetiracetam
pheno decrease leve concentr in a dose dpdt manner
+ more rapid elim (suspicion oxid leve induced by pheno)
CBD: mechanism, first/ ajunct tretment for epil + adverse effects
not canabinoid recep
reduction of presynaptic intracellular calcium concentrations mediated by a functional antagonism at G protein-coupled receptor 55 (GPR55) receptors and a desensitization of transient receptor potential vanilloid 1 (TRPV1) receptors. impact on extracellular adenosine concentrations (impact on calcium and potassium fluxes)
first: 2.5 mg/kg BID, reduction seiz freq 33%
adjunct: 9 mg/kg/d 24% decrease in seizure day
decrease appetite and vomiting, ataxia
increase liver enzyme
phenobarb induced hematol change in cat
75% cytopenia (neutropenia 60%, leukopenia 50%, thrombocytopenia 25%, anemia 20%)
polytherap : lower hematocrite
volumetry change in IE
reduced cingulate gyrus volume
phenobarbarb type 2 reaction
- systemic lupus erythematus:
fever, multiple cytopenia
positive antinuclear AB titer - pseudolymphoma: generalised lymphadenopathy, pyrexia, hepatomeg/splenomeg (histocyt-neutroph inflam)
3-5 weeks after init - pancreatitis, blood dyscrasia, necrolytic dermatitis, dyskinesia
why benzodiazep loss efficacy during prolonged seiz
internalisation GABAa recepty
+ overexp NMDA
risk factor associated with short term mortality and recurrence status
short term mortality (0%) increase age, decreased duration hospit, SE before arrival, SE from fatal etiol
recurrence (30%): history phjaramcoresist, focal
which tube for leve dosage
only serum (in situ hydrolysis in plasma or whole blood)
dermatologic reaction pheno, KBr, zonisamide
pheno: metabolic epidermal necrosis (superficial necrotizing dermtatitis) after several m/y, probably hepatocutaneous
KBr: panniculitis, pustulous derm, non supp white maccules
zonisamide: erythema multiforme
% idiopathic epil dog with hippocampal atrophy
56%
88% same side as temporal epil
effect topical lido application on EEG muscle artifact
not helpful
focal epilepsy with fear-related behaviour:
1. breed
2. associated with … signs
3. histo
4. age of onset
5. antiepil
- boerboel
- autonomic and motor
- vacuoles in the perikaryon in deep cerebal cortical region (pariet, temp, occip)
- 3m
- pheno, KBr
pathol with cerebral vacuoles
- focal epil with fear related behavious in boerboel dogs
- transmissible spongiform encephalopathy
- RABGAPA3 in Alaskan Huskies, Black Russian Terrier, Rottweiler. intracytopl vacuols in cerebellar/BS/thal/SC nuclei. Ataxia, ocular abnom, laryngeal paral
- ATG4D Lagotto Romagnolo. cerebellar ataxia, vacuol cytopl CNS/PNS
- fucosidosis
- GMA gangliosisdosis
- intox
predominant type seiz pomeranian
focal (limb contraction)
juvenile epil Rhodesian % photos
breed with increase frequence status/cluster
cluster + status: Border Collie
Status: Aust Sheperd
IE related death % in italian spinone, Border, Irish Wolfhund, great swiss montain
IT: 32%
Border: 35%
Irish Wolfhund: 52%
great swiss montain: 35%
decrease survival time Border and Aust sheperd if onset < 2y
mutation begnign familial epil lagotto romagnolo + epil assoc with
focal-onset seizures, start 5-9 weeks, spontaneously remit 13 w
LGI2 mut (synapse formation during dev)
Behavioural abn: inattention, excitability impulsivity, event after 4y
% structural epil in Boxer
93% (neoplasia)
most common seiz type in irish setter
generalised
ab in cat limbic encephalitis
seizures type
leucin rich glioma-inactivated I
voltage gated potassium channel
focal seiz, cluster, interictal behaviour change
types of SE
motor: convulsive, myoclonic, focal motor, hyperkinetic
non convulsive: comatose or not comatose
physiopathology of status
5-10 min: impending
neurotransmit release/imbalence
ion channel opening/closure
first line treat
10-30 min: established
GABAaR decrease, inetrnalisation of GABAaR
NMDA and AMPA R upregulation
second>first
> 30 min refractory
excitatory and inhibit neuropeptide realease/imbalance
BBB transporter upregulation
third line treat
> 24h superrefractory
gene exp alteration
1st, 2nd, 3rd line treatment status
1st: mida IN, IV or diazepam IV +/- mida CRI
2nd: leve IV + pheno IV +/- fosphenytoin IV
3rd: ketamine IV +/- dexmedeto, propofol, pentobarb, inhalational anest
action mechanism propofol, dexmedeto, keta
dexmedeto: alpha2 adrnorecept ago ->supression norepi release, decrease cerebral oxygen demand, vasoconstriction brain
propofol: GABAaR, non BZP site + glycine and NMDA antag. Heinz body anemia in cat
inhalant anesth GABAa
anesth barbiturate GABAa
phosphetoin GABAa, NMDA AMPA
elim half life KBr, imepitoin, levet
KBr 15d
imepitoin 2h
levetiracetam 2-4h
zonisamide is metabolised by
+ weak inhib of …
hepatic enzyme CYP3A4
weak carbonic anhydrase inhibitor
coadmn with pheno increase clearance by 50% and shorten elim half life
higher risk idiosynch react if allergic episod with sulfonamide
LGI (leucin rich glioma inactivated) proteins action
LGI1 binds to
1. presyn volt gated k channel Kv1 -> increase Ca influx and neurotrans release
2. presynap ADAM 23 ->affect neurite outgrowth
3. post synap ADAM22 -> stabilised synapse with presyn
4. regulation AMPA -> glutamate recept
LG role in maturation glutaminergic synapse (LGI2 immediately post nat)
pathologies associated with LGI proteins
Lagotto Romagnolo mut LGI2: familial juvenil epil.
Belgian Sheperd ADAM23: predisp adult epil. focal seiz, 3-4y, very low freq SE
limbic seizure in cat: antibodies against VGKC complexes/LGI1
suppression LGI1expression in glioblastoma
transcranial magnet stim act by which neurotransmit
dopamine
ABCB1 gene in epil
Border: assoc ABCB1 and phenobarb resistance in only one variant
medium-chain TG action
elevation beta hydroxybutiric acid (suspected by ATP channel and GABAb)
reduce seizure frequency, better QoL
reduces pheno concent 8%, ALKP 10%
mineral in epileptic dogs
higher Cu, Zn, Se, As
lower P
cardiac troponin 1 and seizure
tropo 1 higher in dogs with recent seiz
associated with : number seiz, age
ammoniema after seizure in cat
transient hyperammonemia
feline temporal lobe epil:
1. equivalent in humans
2. type of seizure
3. localisation
4. causes
- autoimmune limbic encephalitis and temporal lobe epil
- focal, orofacial or head twitching, hypetrsalivation, lip smacking, mydriasis, vocalisation, motionless staring with interict behaviour change
- hippocampus and piriform lobe
- astrocytoma/lymphome, voltage gated potassium channel antibodies (targeting LGI1), DCC: deleted in colorectal carcinome = netrin 1 recept
in cat half life
1. pheno
2. leve
3. zonisamide
4. gaba
5. diazepam
- 40-80h, escalating dose over time is rare in cat
- 3h
- 33h
- 2.5-3.5h
- 15-20h, no functional toler i cat
More often focal/generalised seizures in cat with hypertyroidism/hepatic encephalopathy
focal
feline audiogenic reflex seizure
15y
Birman
levetiracetam
high pitched sound
% IE, structural, reactive seizures in cat
reactive 15-25%
structural 40-70%
idiopath 22-57%
% cat with intracran lymphoma positive for FeLV
18%
causes of ischemic CVA in cat
hypertension (renal, hyperthyroidism)
cuterebra (< 4y, access to outdoor in sumer months)
systemic neoplasia
cardiomyopathy
sepsis
vasculitis
vascular degeneration
thimaine deficiency:
1. localisation
2. causes
3. signs
- lateral geniculate nuclei, caudal colliculi, facial nuclei, cerebellar nodulus, medial vestibular nuclei
- diets preserved with sulfur dioxide, inaquately suppelmented, thimaine degradeds by heating, diet with thiaminase
- imapaired vision, mydriasis, ataxia, ventroflexion, vestibular signs, seizures (60%). 80% of seizuring cat with status/cluster
- salivation during seizure
- ictal vocalisation
in cat is more likely in …
- status/cluster more frequent in IE/struct/react
- IE
- structural epil
- 10-20% in IE vs 40% in other causes, associated with poorer survival
hepatic enz induction with pheno in cat
NO, but some cases of increase ALT
most common adverse effect pheno cat + factors
sedation, ataxia
increase with dose, second AE
% epileptic cat with normal MRI and abnormal CSF
4.6 %
maj cause epil <12m in cat
structural
levetiracetam and pheno + recomanded dose
Phenobarbital significantly decreased serum levetiracetam concentration in a dose dependent manner
levetiracetam dosage of 99–216 mg/kg/day is necessary to obtain a serum levetiracetam concentration of 20 μg/mL when used alone or concurrently with 7 mg/kg/day of phenobarbital
no significant causal link was found between serum phenobarbital concentration and serum levetiracetam concentration
increasing doses of phenobarbital, the correlation between the PO dose of levetiracetam and serum concentrations may disappear
No significant association was found between serum levetiracetam concentration and clinical efficacy.
significant and positive effect of levetiracetam PO dose was observed on serum levetiracetam concentration except in the case of zonisamide dual therapy with levetiracetam
complement C3 and C4 in dogs with idiopathic epilepsy
Serum C3 and C4 concentrations were significantly higher in dogs with IE
No significant differences were observed between dogs in the treatment and nontreatment groups
Dogs with a seizure frequency >3 times/month had significantly higher serum C3 and C4
