Seizure Dr. Sterczer Ágnes associate professor SZIU, Faculty of Veterinary Science, Internal Medicine Department and Clinic.

Seizure Dr. Sterczer Ágnes associate professor SZIU, Faculty of Veterinary Science, Internal Medicine Department and Clinic

Seizure Clinical manifestation of an abnormal neuronal hyperactivity involving the cerebrocortical neurons PATHOPHYSIOLOGY: imbalance between normal excitatory and inhibitory mechanisms Prodrome: Prodrome: ( before seizure). Hiding, attention seeking, whining, agitation Aura: Aura: (initial manifestation of seizure) stereotypical sensory /motor activity: pacing, licking, swallowing. Barking, attention seeking Ictus: ( Ictus: ( seizure itself) loss/derangement of consciousness, altered muscle tone, jaw chomping, salivation, involuntary urination, defecation Postictal period: ( Postictal period: ( disorientation, somnolence, altered thirst etc)

SEIZURE CLASSIFICATION IDIOPATHIC EPILEPSY  primary, idiopathic (genuine) epilepsy  Functional intracranial  no obvious structural brain disease SECONDARY SEIZURE or EPILEPSY  Structural diseases of the brain  structural brain damage caused by infections, trauma, brain malformations, tumors etc  structural brain damage caused by infections, trauma, brain malformations, tumors etc. REACTIVE SEIZURE  Extracranial disease  Normal brain GENERALIZED PARTIAL (focal) simple simplecomplex

GENERALIZED seizure GENERALIZED seizure widespread onset within both cerebral hemisphere loss of consciousness recumbence generalized motor signs, mostly violent motor activity that involves the whole body (convulsions) Tonic (sustained), clonic (repetitive) contractions, limb paddling and trembling, jaw chomping, facial twitching Autonomic hyperactivity: pupillary dilatation, salivation, piloerection, micturiation, defecation Metabolic diseases, toxicosis, IE

GENERALIZED: videó videó

Partial / Focal Partial / Focal focal onset in one cerebral hemisphere focal acquired structural brain lesion Aura (initial portion of seizure) postictal motor deficit (transient localized loss of motor function) Psychomotor seizures (bizarr behaviors) Simple partial: neocortical structures of one hemisphere no consciousness alterations! unilateral motor signs on contralateral to side of the seizure focus Facial twitching, Tonic or clonic movements of one limbs Spasmodic turning of the head to one side

PARTIAL / FOCAL (petit mal) PARTIAL / FOCAL (petit mal) focal onset in one cerebral hemisphere focal acquired structural brain lesion Complex partial: allocortical structures and often continues bilaterally Focal seizures progress to generalized motor seizures Consciousness impared or loss! contralateral or bilateral asymmetric or symmetric motor signs limited to some parts of the body circling, behavioral activities like startling, growling, hissing, chasing often seen in cats Bizarre activity may be seen (psychomotor seizures) Stereotypical (circling) Behavioral (startling, growling, hissing, chasing, attacking objects, fly biting, howling)

Petit mal: videó

SEIZURE Isolated seizure Brief, isolated event, lasting<2 min) „Cluster” seizures >2 over 24-hour period Status epilepticus: Neurologic emergency! continuous clinical seizures lasting at least 10 minutes seizures repeated at brief intervals for >30 minutes without complete recovery of consciousness between individual attacks Convulsive (generalized violent motor activity) Nonconvulsive (milder, subtle motor signs) >20 min irreversible neurologic damage

Common disorders resulting in seizures EXTRACRANIAL DISORDERS 1. Toxins 1. Toxins (Pb, etylenglycol, org.P,metaldehyd, strychnin) 2. Metabolic diseases 2.1. Hypoglycaemia 2.2. Liver diseases HE 2.3. Hypocalcaemia 2.4. Severe uraemia 2.5. Heat stroke 2.6. Diabetic ketoacidosis 2.7. Electrolyte disturbances 2.8. Hyperlipoproteinaemia 2.9. Hyperviscosity (polycitemia) IDIOPATHIC EPILEPSY

EXTRACRANIAL reasons Reactiv epileptic seizures Alter the brain biochemical homeostasis in favor of excitation Endogen/exogen neurotoxins→blood –brain barrier or neurotransmission CS /SE Rapidly recurring seizures may recruit adjacent areas of brain and may produce neuronal damage Consciousness can be changed confusion, delirium, depression

EXTRACRANIAL DISORDERS 1. Toxins (Pb, etylenglycol, org.P,chlorinated hydrocarbons, metaldehyd, strychnin) 2. Metabolic diseases 2.1. Hypoglycaemia 2.2. Liver diseases HE 2.3. Hypocalcaemia 2.4. Severe uraemia 2.5. Heat stroke 2.6. Diabetic ketoacidosis 2.7. Electrolyte disturbances 2.8. Hyperlipoproteinaemia 2.9. Hyperviscosity (polycitemia)

Strychnine Stiff extension of legs and body, tetanic spasms induced by auditory stimuli emesis (if no neurologic signs), gastric lavage, pentobarbital Metaldehyde Snail, rat poison Hyperesthesia, tachycardia, salivation, tremor, nystagmus in cat, respiratory failure, seizure, (not worsened by auditory stimuli) Acetaldehyde odor on breath Gastric lavage, intubation, ventilation, pentobarbital Organophophates, carbamates insecticides Salivation, lacrimation, GI, miosis, twitching facial and tongue muscles, tonic-clonic seizures signs+low serum acetylcholinesterase activity Atropine 0,2 mg/kg iv  sc 3x pralidoxime 20 mg/kg im 2x if <48h or dermal exposure

TOXICOSIS-SEIZURE Chlorinated Hydrocarbons Insecticids, agricultural products, absorbed through skin Hypersensitivity, salivation, muscle twitching of face and neck, tremor, tonic-clonic seizures Insecticide smell to haircoat Wash with warm, soapy water, pentobarbital Lead Abdominal pain, GI, megaesophagus, hysteria-aggression, tremor, seizure, blindness, hypermetria, nystagmus, dementia Rbc:basophylic stippling, nucleated rbc, PB>50 mg/dl Ca-EDTA 25 mg/kg iv 4x (10 mg Ca-EDTA/ml in 5% dextrose) + diuresis! Succimer 10 mg/kg per os 10-14 day Ethylene glycol

Metaldehid ethylenglycol video

Hypoglykaemia Sepsis! Young puppy Glycogen store and impaired metabolism, ascariosis, fasting „Toy breed” Glycogen store, stress, fasting, diarrea Hunting dogs Stress, fastingHyperinsulinaemia Treatment of Diabetes mellitus Insulinoma or other insulin secreting tumors Very severe liver function injury

Hepatic encephalopathy Encephalopathy due to liver failure. Syndrome Acut Acut (6-8%) rare acut, fulminant encephalopathy severe liver necrosis(70-80%) severe brain oedema (glutamin accumulation in the brain) Chronic HE 92-94 % common PSS collateral circulation + decreased liver function! Portosystemic encephalopathy (PSE) congenital/acquaried PSS Cat: Hepatic lipidosis; congenital enzim deficiency of urea c. Failure of the neurotransmitter systems

Hepatic encephalopathy Symptom Episodic, reversible (CPSS), GI : GI : anorexia, weight loss, vomitus, diarrhoea, salivation APSS: more expressed GI: portal hypertension  ascites, oedema, melaena Urinary system ammonium-biurat crystals Urinary system signs 40-50% PU/PD, urat urolithiasis, cystitis, dysuria, stranguria, pollakisuria haematuria, cristalluria, ammonium-biurat crystals CNS CNS signs 80-90% 1-4 grade! Severness not correlate with the ammonia level Episodic, wavy intensity, severityDiagnosis Labor Labor : microcytosis (CPSS), liver enzymes  / , urine: ammonium-biurat crystals (CPSS) Liver function tests Liver function tests : NH 3 (ATT, PPATT) ; FBA-PPBA doppler US CPSS: doppler US, (scintigraphy, porthography)

Hypokalaemia-alkalosis ICEC K↓K↓K↓K↓ K K H +, Na + alkalosisacidosis NH 3 + H + ↔ NH 4 +

hypocalcaemia

Neurologic manifestation of systemic disease Alteration in electrolyte and water balance Secondary cerebrocortical dysfunction Na ↑↓ brain osmolality Ca ↑↓; K ↑↓ effect on ion channels in CNS, lead to excitatory or inhibitory neurotransmission Metabolic disorders Secunder effect on cerebrocortex /thalamusra Endogen neurotoxinsPolycythemia ↑viscosity→↓microcirculation→local hypoxia

INTRACRANIAL DISORDERS(CNS) INTRACRANIAL DISORDERS (CNS) 1. Congenital 1.1. Hydrocephalus 1.2. Lissencephaly 1.3. Cortical dysplasia 2. Neoplasia 3. Inflammatory disease 3.1. Infectious inflammatory disease 3.2. Non infective encephalitis (GME, SRMA.) 4. Vascular disease 4.1. Hemorrhage (coagulopathy, hypertensio) 4.2. hypoxia 4.3. ischaemia 5. Trauma-scar formation 6. Metabolic storage diseses 7. Degenerative conditions

HYDROCEPHALUS Cerebral ventricular system is enlarged sec. to  CSF compression or atrophy of surrounding neurologic tissue. (  ICP) Mostly congenital -enlarged head, palpably open fontanelles -episodes of abnormal behavior/dementia/ cortical blindness, divergent strabismus -tetraparesis/decreased proprioceptions Diagnosis: signs/breed/age/ US/ CT/ EEG

LISSENCEPHALY Sulci and gyri fail to develop normally  smooth cerebral cortex rare! Lhasa Apso (wirehaired Foxterriers/Irish Setters Clin: behavioral abnormalities, visual deficits, difficult to train, seizures Diagnosis: EEG, MRI, Brain biopsy ( slow wave, high voltage over areas of cerebral cortex)

NEOPLASIA Gradual onset of slowly progressive neurologic signs.  ICP Acute signs:if hemorrhage/edema occurs association with tumors Clin: decreased/abnormal response to stimuli, progressive loss of consciousness, change in mentation, dull, depressed, „suddanly old”, seizures, evidence of focal neurologic lesion, circling Diagnosis: CT/ MRI/ X-ray/ liquor CSF: pressure , tumor cell no, CSF cell count , 50-150 WBC/ul mononuclear, protein  (alb  + ,  globulin  tumor) (alb  +  globulin  inflammation) (alb  +  globulin  inflammation)

INFLAMMATORY DISEASES Inflammation  encephalitis  seizures INFECTIOUS inflammatory CNS -acute distemper-FIP -bacterial-FIV -toxoplasmosis-rabies -neosporiosis-Lyme disese -cryptococcosis-Ehrlichiosis -Rocky Mountain spotted fever FIP CSF: nonseptic inflammation, protein , neutrophil, macrophag, lymphocyta  FIV CSF: protein ,lymphocyta ,FIV antibody

STEROID-RESPONSIVE-MENINGO- ARTERITIS SRMA Beagle pain, necrotizing vasculitis, aseptic meningitis Idiopathic reason, immunological cause  vasculitis/arteritis affecting meningeal vessels of spinal cord, brainstem Young dogs (6-18 months) rarely middle-aged Large breeds most commonly (beagle, boxer, german shorthaired pointers, retriever, Bernese Mountain dogs) Clinical signs: Clinical signs: fever, cervical rigidity, wax and wane vertebral pain Acut: ≈meningitis chronic: ≈ spinal cord signs Concurrent immune-mediated polyarthritis (IMPA) Labor:CSF: Labor: neutrophil leucocytosis CSF: protein , >100 cells/ul; >75% ngr High IgA in CSF and blood (acute: ngr, chronic: ly pleocytosis) Prednisolon  CSF normal or mononuclear cells CSF should be collected before therapy Systemic IgA production DD Systemic IgA production DD : GME IgA, IgM produced by nervous s. Therapy: corticosteroid Therapy: corticosteroid tapering If not respond + azathioprine Prognosis: good

Idiopathic inflammatory disorder of CNS in dog Young, adult dogs 2-6 years (Cat NO) small breeds (poodles, terriers) focal/ disseminated/ ocular forms -neurologic dysfunction, severe pain, cervical pain, rain stem signs -brain stem signs: nystagmus, head tilt, blindness, VII, V paralysis, -ataxia, seizures, circling, behavior change inflammatory cell accumulation/proliferation around blood vessels in CNS (perivascular cuff)  (  globulin),  /  pleocytosis ly/mo CSF: protein  (  globulin),  /  pleocytosis ly/mo First exclude the infective causes of ME!! CT contrast enhances mass, dg: biopsy corticosteroid prednisone (cytostatic) corticosteroid prednisone (cytostatic) GRANULOMATOUS MENINGOENCEPHALITIS (GME)

Idiopathic inflammatory disorder of brain in Pugs Necrotizing leucoencephalitis, pug encephalitis Pug, Malteses, Yorkshire Terriers no infective agent, genetic predisposition Necrosis, nonsuppurative necrotizing meningoencephalitis Progressive cerebral cortical disease Seizure, neurologic signs referable to cerebrum and meninges CSF: CSF: protein , nucleated cell count , ly No specific treatment Prognosis: poor NECROTIZING MENINGOENCEPHALITIS (NME)

FELINE POLIOENCEPHALOMYELITIS nonsuppurative encephalomyelitis idiopathic young, adult cats 3 months-6 years -chronic, progressive seizures -spinal cord signs: pelvic limb hyporeflexia ataxia/ paresis of pelvic limbs -intention tremors of the head -behavior change protein  /   mononuclear cells CSF: protein  /   mononuclear cells Definitive diagnosis: necropsy perivascular cuffing with mononuclear cells, ly meningitis, glial nodules, demyelinisation poor prognosis

FELINE ISCHEMIC ENCEPHALOPATHY FIE Cerebral infarct syndrome of unknown etiology middle cerebral artery summer months adult cats peracute onset of asymmetrical neurologic abnormalities: dementia/aggression/circling /seizures/  proprioception, reflexes  in the limbs oppo. cortical blindness (blind, normal pupillary light reflexes) acute onset of nonprog. unilateral cortical diseases, no history of trauma or illness

EPILEPSY Syndrome of recurrent seizures, not associated with progressive IC a) idiopathic/ primer epilepsy inherited functional problem in the brain b) acquired epilepsy cerebral insult  residual brain damage Status epilepticus: life-threatening condition  neuronal damage, systemic complication

IDIOPATHIC EPILEPSY Most common cause of seizures Most common cause of seizures (Cat uncommon) repeated episodes of seizures with no demonstrable cause. Normal between seizures. Seizure threshold ↓ Inherited : LABRADOR, RETRIEVER breed predisposition : Golden retriever, German shepherd, Belgian Tervuren, Keeshond, Beagle, Dachshund, retrievers, collie, irish setter 6 m-5 years (juvenile:8-12w---outgrow by 4-6m) generalized ! tonic-clonic seizures 90% unconsciousness (+psychomotor signs: agression, pacing, hallucination, stargasing, tailchasing) recur at regular intervals with aging frequency/severity of seizures  NORMAL:physical/neurologic/ophtalmologic clinicopathologic tests/ CSF/ interictal EEG Prodromal: aura/preictus-ictus-postictus

ACQUIRED EPILEPSY prior inflamm./traumatic/toxic/metabolic/vascular INSULT alters a focus of neurons  seizure Usually frontal/temporal lobe Usually partial! Seizure (no uncosciousness) any age/ any breed, either gender dogs/cats usually can not be determined the cause ABNORMAL:physical/neurologic/ophtalmologic al/clinicopathologic tests/ CSF EEG may be abnormal No prodromal phase (aura/ictus) Progressive: seizures more frequent/intens/longer

DIAGNOSIS Seizures

Nationale Species, breed, age, sex History/ Decursus vaccination, toxin, trauma, drugs, other previous diseases seizure: form, type,description (video), onset, duration, frequency, present before, day time, signs between two seizure Other complains, clinical signs Physical-Ophthalmological-Neurological examination mm, BCV (temperature, pulse, breathing) Emergency neurology: consciousness, pupil (size, PLR, symmetricy), eye position, nystagmus, motor function (posture, position of head, ataxia, paresis, reflexes) cranial reflexes, skull, ear Respiratory alterations Labor examinations (screening test) Instrumental examinations

Laboratory test (screening tests) Next the animal: blood glucose!!!! cystocentesis CBC CBC (qualitative, quantitative) Usually not characteristic leucocytosis-inflammatory disease leucocytosis left shift-bacterial meningoencephalitis lymphopenia-acute viral infection microcytosis with or without thrombocytopenia- PSSBiochemistry Liver: ALT, GGT, ALP, BA, (NH3), TP, alb Kidney: Urea, creatinine, P Ionogram: Ca, K, Na acid-base Serology serologic tests (FeLV/FIV, distemper, toxoplasma) Immunology (?) IC, ANA

Laboratory tests Urinalysis: Urinalysis: -specific gravidity -protein -glucose -ketone -crystalls: Oxalat: ethylenglycol-toxicosis ammonium biurate: PSS

Instrumental examinations CSF (liquor) CSF (liquor) colour, átlátszóság protein, enzyme activity glucose, electrolyte cell number microorganisms Contraindikation: coagulopathy, increased ICP

Instrumental US: brain, abdomen (liver, kidney, pancreas) X-RayEEGCTMR

TREATMENT Status epilepticus ICP

STATUS EPILEPTICUS Series of seizures without periods of intervening consciousness medical emergency  immediate seizure control is required! seizure>20’ result in permanent neuronal damage systemic effects of status epilepticus: -hyperthermia -lactic acidosis -hypoxemia -cardiac arrythmias -pulmonary edema -death

Treatment – in seizing animal in status epilepticus  Iv catheter insert Immediately stop ongoing seizures  Diazepam  Diazepam iv. (0.5-1,0 mg/kg dog 0.5 mg/kg cat)  If 2-3’ not effect→ repeat 2-4x 10’ max 3 mg/kg  2 mg/kg rectally if not iv catheter  Maintain airway  Maintain airway, intubation, oxygen, hyperventilation  Pentobarbital-Na  Pentobarbital-Na (5-15 mg/kg iv. slowly, to effect)  If diazepam not effective repeatedly, or seizure reoccur  Propofol  Propofol (1-4-(8) mg/kg iv slowly, to effect)  Temperature 38-39.5C  ICP  Blood sampling

Treatment – in seizing animal in status epilepticusban Prevent seizure recurrence over following hours  Phenobarbital  Phenobarbital (2-4 mg/kg iv/im 2x)  Loading dose: 15-25 mg/kg [PB=80-110 umol/l]  Maintain dose (2-2.5 mg 2x)  Diasepam inf  Diasepam inf. (0.5 mg/kg/h in salsol inf (KBr!))  Adsorbed to plastic, inactivated by light, prepare only 1-2 hours solution  If >20’ since last bolus, start with bolus again beginning of infusion, than maintained by infusion  If no seizure for 4-6 h →↓ 25% dose /4-6 h  If >2 seizure during infusion→bolus, ↑1.5 mg/kg/h inf  If inf not possible: 0.5 boluses iv q20’ 4-5x  Pentobarbital inf  Pentobarbital inf (2-5 mg/kg/h iv slowly, to effect)

Treatment – in seizing animal in status epilepticusban Control refractory seizures  Propofol  Loading dose: 1-3.5 mg/kg to effect  Maintenance infusion (0.01-0.25 mg/kg/min 6-24 h  General anesthesia  Propofol  Propofol: bolus 4-6 mg/kg →maintain 0.1-0.3 mg/kg/min  Isofluran  Pentobarbital iv bolus 2-5 mg/kg  Pentobarbital iv bolus 2-5 mg/kg →maintain 5 mg/kg/h  Monitoring:intubation, respiration, ventilation, hypotension Treatment of CS at home  Rectally diazepam 1 mg/kg (2. seizure/12-24h) 3-4x repeated q 20’. If >2 seizure recur despite this treatment  Rectally diazepam 1 mg/kg (2. seizure/12-24h) 3-4x repeated q 20’. If >2 seizure recur despite this treatment → hospital

ICP, cerebral edema OXYGEN avoid HYPOXEMIA! PaO 2 >90 Hgmm Sat>97% PaCO 2 30-40 Hgmm Oxygen cage, mask (intranasal/intratracheal NO---may cause sneezing, coughing  temporary ICP  ) If insufficient oxygenation  intubation, PP ventillation Hypoventilation:PaCO 2  (>40 Hgmm)  respiratoric acidosis  cranial vasodilatation  CBF  ICP  Hyperventilation:PaCO 2  (<30 Hgmm)  respiratoric alkalosis  cranial vasoconstriction  CBF   cerebral ischemia Short period HYPERVENTILATION

ICP, cerebral edema FLUID THERAPY!!!! Tissue perfusion, blood pressure Euvolemia!!! Avoid:overhydration, or restriction Euvolemia!!! Avoid:overhydration, or restriction (hypovol, ischemia) Isotonic crystalloid, colloid, blood No:hypotonic solution (5% Dextrose, 0,45 % NaCl) IC  cerebral edema IC  cerebral edema  MANNIT! 0,5-1 g/kg 20’ MANNIT! 0,5-1 g/kg 20’ 4-8h repeat 1-3x Not proved that, increase intracranial hemorrhagia (more benefit than risk) Osmotic, „antioxidant”, cerebral microcirculation  In euvolemia !!! (ozm.diuresis  intravasc. volumen  cerebral perfusion  ) FUROSEMID?? HYPERTONIC SALTS 7,5 % NaCl 4 ml/kg 15’ In hypovolemia !!! (quickly restore the euvolemia)

ICP, cerebral edema CORTICOSTEROID Not suggested! May be in brain edema associated tumor??? MetilprednisolonDexamethasoneMetilprednisolon 30 mg/kg iv or Dexamethasone 1 mg/kg iv ELEVATION of the HEAD 15-30° avoidance of pressure on the v. jugular B 1 vitamin 2 mg/kg im ? ANALGEZIA in case of trauma Butorphanol, hydromorphine Avoid: Ketamine/ acepromazine/ xylazine Influance the cerebral blood pressure and the metabolic stage

Per os antiepileptic treatment If the seizures more frequent than 3-4 /months (4 times/year) If treated early in the course, may have better long term control After a severe or cluster seizures, status epilepticus Seizure caused by intracranial lesion Seizures becoming more frequent Severe postictal signs Requirements for antiepileptic drugs: - effective, without remarkable side effects, - providing continuous, effective anticonvulsive blood level, - practical application (per os/8 hours) Client education Monitoring: blood labor (Ph/Kbr) monitoring Liver function, screening biochemistry

Antiepileptic treatment Couto 2009 Phenobarbital Phenobarbital 2 mg/kg po 2x if seizure continue 48h : 4 mg/kg po 2x 10-14 days: serum [Ph]<20 ug/ml  25%  repeat until: 25-35 ug/ml (86-130 umol/l) If ok, control 2x /year [Ph] if seizure continue: max (4 h post tabl)/ min (pre tabl) if  25% Ph 3x if seizure continues:[Ph] 30-35 ug/ml (130-150) +KBr if seizure continues: + KBr 15 mg/kg 2x if no seizure, but sedated  20% Ph if seizure continues:  KBr 20 mg/kg 2x serum [KBr] 3 months=10-20 mmol/l (1-2 mg/ml)

Anticonvulsant treatment Ettinger 2005 A) KBr 40-50 mg/kg A) KBr 40-50 mg/kg po 1x  Steady state concentration20-25 mmol/l (2-2,5 mmol/l)  Steady state concentration (3 months) 20-25 mmol/l (2-2,5 mmol/l) If >1 seizure/6-8 week or there is seizure inspite of [Br]=20-25 + Phenobarbital 2,5-4 mg/kg 2x  Optimal blood level20-30 mg/ml ( 86-130 umol/l)  Optimal blood level 20-30 mg/ml ( 86-130 umol/l) B) KBr 60-80 mg/kg po 2x 5 days starter dose (30 mg/kg 4x) than 15 mg/kg 2x maintenance dose C) If seizure <3-4 week and SE/CS:  KBr 100-300 mg/kg in 4 parts  From next day 40-50 mg/kg 1x CAT  Phenobarbital 2-2,5 mg/kg 2x  Diazepam 0,5-1 mg/kg 2x Aim in 5 days 500-800 ng/ml= nmol/l

PHENOBARBITAL 2-5 mg/kg 12h Steady state blood concentration in 10-15 days Peak in 4-(8) hours after oral administration Therapeutic range: dog: 25-35 ug/ml Therapeutic range: (avoid serum separator tube) dog: 25-35 ug/ml (107-150 umol/l) cat: 10-30 ug/ml ( 45-129 umol/l) If blood Ph low  25%  Relatively safe, effective, well-tolerated, inexpensive Adverse effect: PU/PD, sedation, depression, hyperexcitability, rarely leukopenia Microsomal enzyme induction in the liver, (hepatotoxicus) not in cat! Easy to addict, can not be interrupted quickly Drugs, inhibit the microsomal enzymes in the liver: (TC, ranitidin, cimetidin, enilkonazol), decrease the liver metabolism of the Ph----  [Ph]

KBr Metabolised through the kidney, no hepatotoxic 20-40 mg/kg (monotherapy) 15 mg/kg 2x (add-on drug) Therapeutic blood level 3 months [KBr] 1,5-2.3 mg/ml (15-23 mmol/l) (monotherapy) 1-2 mg/ml (10-20 mmol/l (together with Ph) T 1/2 =25 days dog T 1/2 =11 days cat Effective as a single agent (monotherapy) Initial drug Ph + KBr decreasing seizures number Ph + KBr decreasing seizures number Not to cats: feline asthma, bronchitis Br excretion by kidneys proportional with Cl intake!  dietary Cl, vagy NaCl infusion   Br elimination from serum  Br  Adverse effects: PU/PD, polyphagia, sedation, incoordination, constipation Hyperosmol---gastric irritation---vomitus (in more parts,with food) No A.U.V. form (except Crisax), magistral Very cheep, wide therapic range!

DIAZEPAM Dog : - very short half-life expensive - status epilepticus - its metabolit is also anticonvulsant, - tolerance to anticonvulsive effect can be developed - blood therapeutic: 200-500 ng/ml - before/after seizure 1-2 mg rectally:  severity,  risk of status epilepticus -plastic absorbes the drug -preictal or aura: 2 mg/kg rectally -plastic absorbes the drug -preictal or aura: 2 mg/kg rectally decreases occurrence of CS /SE Cat: - longterm treatment also possible! - longer T1/2 - 2. choice followed Ph - 2. choice followed Ph - optimal blood level: 500-800 ng/ml - optimal blood level: 500-800 ng/ml -idiosyncratic hepatoxicity -idiosyncratic hepatoxicity

FELBAMATE Effective in dogs in focal seizure! alone or add-on (PB or KBr) 70% urinary excretion than by hepatic metabolism (P450) 15 mg/kg q8h (wide margin safety, can be  to 70 mg/kg q8h ) Therapeutic serum level: 25-100 mg/l Does not cause sedation ZONISAMIDE Sulfonamide-based, suppresses epileptic foci and blocks the propagation of epileptic discharges Well absorbed, hepatically metabolized, long T1/2 (15h) alone or add-on Well tolerated with very few side-effects 5-10 mg/kg q12h (if not PB) 10 mg/kg q12h with PB Therapeutic serum level: 10-40 ug/ml Very expensive LEVETIRACETAM LEVETIRACETAM Effective anticonvulsant in dogs and cats! „LEV-binding places” alone or add-on (PB or KBr) Well absorbed, rapidly metabolized, T1/2 (3-4h), excreted unchanged in urine 10-20 mg/kg q8h (wide margin safety) expensive

GABAPENTIN Well absorbed, renally excreted, T1/2 (3-4h)! (3-4x/day) add-on drug Well tolerated with very few side-effects 10-20 mg/kg q8h (if not PB) (  80 mg/kg q6h) Therapeutic serum level: 4-16 mg/l CLORAZEPATE (Rivotril) Benzodiazepin (bit more prolonged action than diazepam. Shared metabolites with diazepam) Sole or add-on drug Tolerance can be developed. Withdrawal seizure activity Adverse effects: sedation, ataxia, cats: hepatic necrosis 1-2 mg/kg q12h Therapeutic serum level: 300-500 ng/ml PRIMIDON (not suggested) PRIMIDON (not suggested) Phenobarbital + pirimidone/ pirimidone alone Ph  by 60 mg / 250 mg pirimidon pirimidon: 10 mg/kg 3x (never be the first choice) Pi------Ph + PEMA (phenylethylmalonamide) Only in dog (cat NO) Hepatotoxic

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Seizure Dr. Sterczer Ágnes associate professor SZIU, Faculty of Veterinary Science, Internal Medicine Department and Clinic.

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Seizure Dr. Sterczer Ágnes associate professor SZIU, Faculty of Veterinary Science, Internal Medicine Department and Clinic.

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