Seizure

SeizureSeizure

Dr. Sterczer Ágnes associate professor

SZIU, Faculty of Veterinary Science, Internal Medicine Department and Clinic

SeizureSeizure Clinical manifestation of an abnormal neuronal hyperactivity involving the cerebrocortical neuronsPATHOPHYSIOLOGY:PATHOPHYSIOLOGY: imbalance between imbalance between normal excitatory and inhibitory mechanismsnormal 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 CLASSIFICATIONSEIZURE CLASSIFICATION

IDIOPATHIC EPILEPSYIDIOPATHIC EPILEPSY primary, idiopathic (genuine) epilepsyprimary, idiopathic (genuine) epilepsy Functional intracranialFunctional intracranial no obvious structural brain diseaseno obvious structural brain disease

SECONDARY SEIZURE or EPILEPSYSECONDARY SEIZURE or EPILEPSY Structural diseases of the brainStructural diseases of the brain structural brain damage caused by infections, trauma,structural brain damage caused by infections, trauma, brain brain

malformationsmalformations, tumors etc, tumors etc.

REACTIVE SEIZUREREACTIVE SEIZURE Extracranial diseaseExtracranial disease Normal brainNormal brain

GENERALIZEDGENERALIZEDPARTIAL (focal)PARTIAL (focal)

simplesimplecomplexcomplex

GENERALIZED GENERALIZED seizureseizure widespread onset within both cerebral hemispherewidespread onset within both cerebral hemisphere

loss of consciousnessloss of consciousness

recumbencerecumbence

generalized motor signs, mostly violent motor generalized motor signs, mostly violent motor activity that involves the whole body activity that involves the whole body (convulsions) (convulsions)

Tonic (sustained), clonic (repetitive) contractions, limb paddling and trembling, jaw chomping, facial twitching

Autonomic hyperactivity: pupillary dilatation, Autonomic hyperactivity: pupillary dilatation, salivation, piloerection, micturiation, defecationsalivation, piloerection, micturiation, defecation

Metabolic diseases, toxicosis, IEMetabolic diseases, toxicosis, IE

GENERALIZED: videóGENERALIZED: videó

videó13Epilepsy-grand mal-kuty.WMV

PPartial / Focalartial / Focal focal onset in one cerebral hemispherefocal onset in one cerebral hemispherefocal acquired structural brain lesionfocal acquired structural brain lesionAura (initial portion of seizure)Aura (initial portion of seizure)postictal motor deficit (transient localized loss of motor postictal motor deficit (transient localized loss of motor function)function)Psychomotor seizures (bizarr behaviors) Psychomotor seizures (bizarr behaviors)

Simple partialSimple partial:: neocneocortical structures of one ortical structures of one hemispherehemisphereno consciousness alterationsno consciousness alterations!!unilateral motor signs on contrunilateral motor signs on contraalateral to side of the lateral to side of the seizure focusseizure focus

Facial twitching, Facial twitching, Tonic or clonic movements of one limbsTonic or clonic movements of one limbsSpasmodic turning of the head to one sideSpasmodic turning of the head to one side

PARTIALPARTIAL / FOCAL / FOCAL (petit mal) (petit mal)focal onset in one cerebral hemispherefocal onset in one cerebral hemispherefocal acquired structural brain lesionfocal acquired structural brain lesion

Complex partialComplex partial:: allocortical allocortical structures structures and and often often continues bilaterallycontinues bilaterallyFocal seizures progress to generalized motor seizuresFocal seizures progress to generalized motor seizuresConsciousnessConsciousness impared or loss! impared or loss!contralateral or bilateral asymmetric or symmetric motor contralateral or bilateral asymmetric or symmetric motor signs limited to some parts of the body signs limited to some parts of the body

circling, behavioral activities like startling, growling, circling, behavioral activities like startling, growling, hissing, chasing often seen in catshissing, chasing often seen in cats

Bizarre activity may be seen (psychomotor seizures)Bizarre activity may be seen (psychomotor seizures)Stereotypical Stereotypical (circling)(circling)Behavioral Behavioral (startling, growling, hissing, chasing, attacking (startling, growling, hissing, chasing, attacking objects, fly biting, howling)objects, fly biting, howling)

Petit mal: videó

12Epilepsy-petit mal-kutya.WMV

SEIZURESEIZURE

Isolated seizureIsolated seizure Brief, isolated event, lasting<2 min)Brief, isolated event, lasting<2 min)

„„Cluster” seizuresCluster” seizures >2 over 24-hour period >2 over 24-hour period

Status epilepticus: Status epilepticus: Neurologic emergency!Neurologic emergency!continuous clinical seizures lasting at least continuous clinical seizures lasting at least 110 0 minutesminutesseizures repeated at brief intervals for seizures repeated at brief intervals for >>30 minutes 30 minutes without complete recovery of consciousness between without complete recovery of consciousness between individual attacksindividual attacks Convulsive (generalized violent motor activity)Nonconvulsive (milder, subtle motor signs)>20 min irreversible neurologic damage

Common disorders resulting in seizuresEXTRACRANIAL DISORDERSEXTRACRANIAL DISORDERS

1. 1. ToxinsToxins (Pb, etylenglycol, org.P,metaldehyd, strychnin)

2. Metabolic diseases2. Metabolic diseases2.1. Hypoglycaemia2.2. Liver diseases HE2.3. Hypocalcaemia2.4. Severe uraemia2.5. Heat stroke2.6. Diabetic ketoacidosis2.7. Electrolyte disturbances2.8. Hyperlipoproteinaemia2.9. Hyperviscosity (polycitemia)

IDIOPATHIC EPILEPSYIDIOPATHIC EPILEPSY

EXTRACRANIAL reasonsEXTRACRANIAL reasonsReactiv epileptic seizures

Alter the brain biochemical homeostasis in favor of excitation

Endogen/exogen neurotoxins→blood –brain barrieror neurotransmission

CS /SERapidly recurring seizures may recruit adjacent areas of brain and may produce neuronal damage

Consciousness can be changedconfusion, delirium, depression

EXTRACRANIAL DISORDERSEXTRACRANIAL DISORDERS 1. 1. ToxinsToxins (Pb, etylenglycol, org.P,(Pb, etylenglycol, org.P,chlorinated chlorinated

hydrocarbons, hydrocarbons, metaldehyd, strychnin)metaldehyd, strychnin)

2. Metabolic diseases2. Metabolic diseases2.1. Hypoglycaemia2.2. Liver diseases HE2.3. Hypocalcaemia2.4. Severe uraemia2.5. Heat stroke2.6. Diabetic ketoacidosis2.7. Electrolyte disturbances2.8. Hyperlipoproteinaemia2.9. Hyperviscosity (polycitemia)

StrychnineStrychnineStiff extension of legs and body, tetanic spasms induced by Stiff extension of legs and body, tetanic spasms induced by auditory stimuliauditory stimuliemesis (if no neurologic signs), gastric lavage, pentobarbitalemesis (if no neurologic signs), gastric lavage, pentobarbital

MetaldehydeMetaldehydeSnail, rat poisonSnail, rat poisonHyperesthesia, tachycardia, salivation, tremor, nystagmus in Hyperesthesia, tachycardia, salivation, tremor, nystagmus in cat, respiratory failure, seizure, (not worsened by auditory cat, respiratory failure, seizure, (not worsened by auditory stimuli)stimuli)Acetaldehyde odor on breathAcetaldehyde odor on breathGastric lavage, intubation, ventilation, pentobarbitalGastric lavage, intubation, ventilation, pentobarbital

Organophophates, carbamatesOrganophophates, carbamatesinsecticidesinsecticidesSalivation, lacrimation, GI, miosis, twitching facial and Salivation, lacrimation, GI, miosis, twitching facial and tongue muscles, tonic-clonic seizurestongue muscles, tonic-clonic seizuressigns+low serum acetylcholinesterase activitysigns+low serum acetylcholinesterase activityAtropine 0,2 mg/kg iv Atropine 0,2 mg/kg iv sc 3x sc 3xpralidoxime pralidoxime 20 mg/kg im 2x if <48h or dermal exposure20 mg/kg im 2x if <48h or dermal exposure

TOXICOSIS-SEIZURETOXICOSIS-SEIZURE

Chlorinated HydrocarbonsChlorinated HydrocarbonsInsecticids, agricultural products, absorbed through skinInsecticids, agricultural products, absorbed through skinHypersensitivity, salivation, muscle twitching of face and Hypersensitivity, salivation, muscle twitching of face and neck, tremor, tonic-clonic seizuresneck, tremor, tonic-clonic seizuresInsecticide smell to haircoatInsecticide smell to haircoatWash with warm, soapy water, pentobarbitalWash with warm, soapy water, pentobarbital

LeadLeadAbdominal pain, GI, megaesophagus, hysteria-aggression, Abdominal pain, GI, megaesophagus, hysteria-aggression, tremor, seizure, blindness, hypermetria, nystagmus, dementiatremor, seizure, blindness, hypermetria, nystagmus, dementiaRbc:basophylic stippling, nucleated rbc , PB>50 mg/dl Rbc:basophylic stippling, nucleated rbc , PB>50 mg/dl Ca-EDTA 25 mg/kg iv 4x Ca-EDTA 25 mg/kg iv 4x (10 mg Ca-EDTA/ml in 5% dextrose)(10 mg Ca-EDTA/ml in 5% dextrose) + diuresis!+ diuresis!Succimer 10 mg/kg per os 10-14 daySuccimer 10 mg/kg per os 10-14 day

Ethylene glycolEthylene glycol

Metaldehid Metaldehid ethylenglycolethylenglycolvideovideo



2. Metabolic diseases2. Metabolic diseases2.1. Hypoglycaemia2.1. Hypoglycaemia2.2. Liver diseases HE2.3. Hypocalcaemia2.4. Severe uraemia2.5. Heat stroke2.6. Diabetic ketoacidosis2.7. Electrolyte disturbances2.8. Hyperlipoproteinaemia2.9. Hyperviscosity (polycitemia)

HypoglykaemiaHypoglykaemia

Sepsis!Sepsis!Young puppyYoung puppy

Glycogen store and impaired metabolism, ascariosis, fasting

„„Toy breed”Toy breed”Glycogen store, stress, fasting, diarrea

Hunting dogsHunting dogsStress, fasting

HyperinsulinaemiaHyperinsulinaemiaTreatment of Diabetes mellitus Insulinoma or other insulin secreting tumors

Very severe liver function injuryVery severe liver function injury



2. Metabolic diseases2. Metabolic diseases2.1. Hypoglycaemia2.2. Liver diseases HE2.2. Liver diseases HE2.3. Hypocalcaemia2.4. Severe uraemia2.5. Heat stroke2.6. Diabetic ketoacidosis2.7. Electrolyte disturbances2.8. Hyperlipoproteinaemia2.9. Hyperviscosity (polycitemia)

Hepatic encephalopathyHepatic encephalopathyEncephalopathy due to liver failure. Syndrome

AcutAcut (6-8%) rareaaccut, fulminut, fulminant ant encephalopathencephalopathyy severe liver necrosis(70-80%) severe liver necrosis(70-80%) severesevere brain oedema brain oedema ((glutamin accumulation in the brainglutamin accumulation in the brain))

ChronicChronic HE HE 9 92-94 2-94 % % commoncommon

PSS collateral circulation + decreased liver function!PSS collateral circulation + decreased liver function!

Portosystemic encephalopathy (PSE)Portosystemic encephalopathy (PSE)congenital/acquaried PSScongenital/acquaried PSSCat: Hepatic lipidosis; congenital enzim deficiency of urea c.Cat: Hepatic lipidosis; congenital enzim deficiency of urea c.

Failure of the neurotransmitter systems

Hepatic encephalopathyHepatic encephalopathySymptomSymptom

Episodic, reversibleEpisodic, reversible (CPSS), (CPSS),

GIGI:: anorexia, weight loss, vomitus, diarrhoea, salivation APSS: more expressed GI: portal hypertensionascites, oedema, melaena

Urinary systemUrinary system signs 40-50%PU/PD, urat urolithiasis, cystitis, dysuria, stranguria, pollakisuria haematuria, cristalluria, ammammoonium-biurat nium-biurat crystals crystals

CNSCNS signs 80-90% 1-4 grade!

Severness not correlate with the ammonia levelEpisodic, wavy intensity, severity

DiagnosisDiagnosisLaborLabor: microcytosis (CPSS), liver enzymes /, urine: ammonium-biurat crystals (CPSS)

Liver function testsLiver function tests: NH3 (ATT, PPATT) ; FBA-PPBA

CPSS: doppler USdoppler US, (scintigraphy, porthography)

Hypokalaemia-alkalosisHypokalaemia-alkalosis

IC ECECKK↓↓

K KK

HH++, Na, Na++

alkalosisalkalosisacidosisacidosis

NHNH33 + H+ H++↔ NH↔ NH44++



2. Metabolic diseases2. Metabolic diseases2.1. Hypoglycaemia2.2. Liver diseases HE2.3. Hypocalcaemia2.3. Hypocalcaemia2.4. Severe uraemia2.5. Heat stroke2.6. Diabetic ketoacidosis2.7. Electrolyte disturbances2.8. Hyperlipoproteinaemia2.9. Hyperviscosity (polycitemia)

hypocalcaemia

14Hypocalcaemia-dog.WMV

15Hypocalcaemia-macska.WMV 14Hypocalcaemia-dog.WMV



2. Metabolic diseases2. Metabolic diseases2.1. Hypoglycaemia2.2. Liver diseases HE2.3. Hypocalcaemia2.4. Severe uraemia2.5. Heat stroke2.6. Diabetic ketoacidosis2.7. Electrolyte disturbances2.7. Electrolyte disturbances2.8. Hyperlipoproteinaemia2.8. Hyperlipoproteinaemia2.9. Hyperviscosity (polycitemia)2.9. Hyperviscosity (polycitemia)

Neurologic manifestation of systemic disease

Alteration in electrolyte and water balanceAlteration in electrolyte and water balanceSecondary cerebrocortical dysfunctionNa ↑↓ brain osmolalityCa ↑↓; K ↑↓ effect on ion channels in CNS, lead to excitatory or inhibitory neurotransmission

Metabolic disordersMetabolic disordersSecunder effect on cerebrocortex /thalamusraEndogen neurotoxins

PolycythemiaPolycythemia ↑viscosity→↓microcirculation→local hypoxia

INTRACRANIAL DISORDERSINTRACRANIAL DISORDERS (CNS)(CNS)1. Congenital

1.1. Hydrocephalus1.2. Lissencephaly1.3. Cortical dysplasia

2. Neoplasia3. Inflammatory disease

3.1. Infectious inflammatory disease3.2. Non infective encephalitis (GME, SRMA.)

4. Vascular disease4.1. Hemorrhage (coagulopathy, hypertensio)4.2. hypoxia 4.3. ischaemia

5. Trauma-scar formation6. Metabolic storage diseses7. Degenerative conditions

HYDROCEPHALUSHYDROCEPHALUS

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

LISSENCEPHALYLISSENCEPHALY

Sulci and gyri fail to develop normally smooth cerebral cortexrare!Lhasa Apso (wirehaired Foxterriers/Irish Setters

Clin: behavioral abnormalities, visual deficits, difficult to train, seizuresDiagnosis: EEG, MRI, Brain biopsy(slow wave, high voltage over areas of cerebral cortex)

NEOPLASIANEOPLASIAGradual onset of slowly progressive neurologic Gradual onset of slowly progressive neurologic signs.signs. ICPICP

Acute signs:if hemorrhage/edema occurs Acute signs:if hemorrhage/edema occurs association with tumorsassociation with tumorsClin:Clin:decreased/abnormal response to stimuli, decreased/abnormal response to stimuli, progressive loss of consciousness, change in progressive loss of consciousness, change in mentation, dull, depressed, „suddanly old”, seizures, mentation, dull, depressed, „suddanly old”, seizures, evidence of focal neurologic lesion, circlingevidence of focal neurologic lesion, circlingDiagnosis: Diagnosis: CT/ MRI/ X-ray/ CT/ MRI/ X-ray/ liquor CSFliquor CSF:: pressure pressure, tumor cell no, CSF cell count, tumor cell no, CSF cell count, , 50-150 WBC/ul mononuclear,50-150 WBC/ul mononuclear,proteinprotein (alb (alb+ + , , globulin globulin tumor) tumor)

(alb(alb+ + globulin globulin inflammation) inflammation)

INFLAMMATORY DISEASESINFLAMMATORY DISEASESInflammationInflammation encephalitis encephalitis seizures seizuresINFECTIOUS inflammatory CNSINFECTIOUS inflammatory CNS-acute distemper-acute distemper -FIP-FIP-bacterial-bacterial -FIV-FIV-toxoplasmosis-toxoplasmosis -rabies-rabies-neosporiosis-neosporiosis -Lyme disese-Lyme disese-cryptococcosis-cryptococcosis -Ehrlichiosis-Ehrlichiosis-Rocky Mountain spotted fever-Rocky Mountain spotted feverFIP FIP CSF: CSF:nonseptic inflammation, proteinnonseptic inflammation, protein,,

neutrophil, macrophag, lymphocyta neutrophil, macrophag, lymphocytaFIV FIV CSF: CSF:proteinprotein,lymphocyta,lymphocyta,FIV antibody,FIV antibody

STEROID-RESPONSIVE-MENINGO-STEROID-RESPONSIVE-MENINGO-ARTERITIS SRMAARTERITIS SRMA

Beagle pain, necrotizing vasculitis, aseptic meningitisBeagle pain, necrotizing vasculitis, aseptic meningitisIdiopathic reasonIdiopathic reason, immunological cause, immunological causevasculitis/arteritis vasculitis/arteritis affecting meningeal vessels of spinal cord, brainstemaffecting meningeal vessels of spinal cord, brainstemYoung dogs (6-18 months) rarely middle-agedLarge breeds most commonly (beagle, boxer, german shorthaired pointers, retriever, Bernese Mountain dogs)Clinical signsClinical signs:: fever, cervical rigidity, wax and wane vertebral pain

Acut: ≈meningitis chronic: ≈ spinal cord signsConcurrent immune-mediated polyarthritis (IMPA)

Labor:Labor: neutrophil leucocytosis CSF: CSF: protein, >100 cells/ul; >75% ngrHigh IgA in CSF and blood (acute: ngr, chronic: ly pleocytosis)Prednisolon CSF normal or mononuclear cellsCSF should be collected before therapy

Systemic IgA productionSystemic IgA production DDDD: GME IgA, IgM produced by nervous s.Therapy:Therapy: corticosteroid corticosteroid tapering

If not respond + azathioprinePrognosis:Prognosis: good good

Idiopathic inflammatory disorder of CNS in dogIdiopathic inflammatory disorder of CNS in dogYoung, adult dogs 2-6 years (Cat NO)small breeds (poodles, terriers)focal/ disseminated/ ocular formsfocal/ disseminated/ ocular forms

-neurologic dysfunction, severe pain, cervical pain, -brain stem signsrain 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)CSF: protein ( ( globulin), globulin), / / pleocytosis ly/mo pleocytosis ly/moFirst exclude the infective causes of ME!!First exclude the infective causes of ME!!CT contrast enhances mass, dg: biopsyCT contrast enhances mass, dg: biopsy corticosteroid prednisone (cytostatic)corticosteroid prednisone (cytostatic)

GRANULOMATOUS GRANULOMATOUS MENINGOENCEPHALITIS (GME)MENINGOENCEPHALITIS (GME)

Idiopathic inflammatory disorder of brain in PugsIdiopathic inflammatory disorder of brain in PugsNecrotizing leucoencephalitis, pug encephalitis

Pug, Malteses, Yorkshire TerriersPug, Malteses, Yorkshire Terriersno infective agent, genetic predispositionNecrosis, nonsuppurative necrotizing Necrosis, nonsuppurative necrotizing meningoencephalitismeningoencephalitis

Progressive cerebral cortical diseaseProgressive cerebral cortical diseaseSeizure, neurologic signs referable to cerebrum and Seizure, neurologic signs referable to cerebrum and meningesmeninges

CSF:CSF: protein, nucleated cell count, lyNo specific treatmentPrognosis: poorPrognosis: poor

NECROTIZING NECROTIZING MENINGOENCEPHALITIS (NME)MENINGOENCEPHALITIS (NME)

FELINE POLIOENCEPHALOMYELITISFELINE POLIOENCEPHALOMYELITIS

nonsuppurative encephalomyelitisidiopathic 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 changeCSF: protein protein // mononuclear cellsmononuclear cellsDefinitive diagnosis: necropsyDefinitive diagnosis: necropsyperivascular cuffing with mononuclear cells, ly perivascular cuffing with mononuclear cells, ly meningitis, glial nodules, demyelinisationmeningitis, glial nodules, demyelinisationpoor prognosispoor prognosis

FELINE ISCHEMIC FELINE ISCHEMIC ENCEPHALOPATHY FIEENCEPHALOPATHY FIE

Cerebral infarct syndrome of unknown etiologyCerebral infarct syndrome of unknown etiologymiddle cerebral arterymiddle cerebral arterysummer months adult catssummer months adult catsperacute onset of asymmetrical neurologic abnormalities:peracute onset of asymmetrical neurologic abnormalities:dementia/aggression/circling /dementia/aggression/circling /seizures/ seizures/ proprioception, reflexesproprioception, reflexes in the limbs oppo. in the limbs oppo. cortical blindness (blind, normal pupillary cortical blindness (blind, normal pupillary light reflexes)light reflexes)

acute onset of nonprog. unilateral cortical acute onset of nonprog. unilateral cortical diseases, no history of trauma or illnessdiseases, no history of trauma or illness

EPILEPSYEPILEPSYSyndrome of recurrent seizures, Syndrome of recurrent seizures, not associated with progressivenot associated with progressive IC IC a) idiopathic/ primer epilepsya) idiopathic/ primer epilepsy

inherited functional problem in the braininherited functional problem in the brain

b) acquired epilepsyb) acquired epilepsycerebral insultcerebral insultresidual brain damageresidual brain damage

Status epilepticus:Status epilepticus:life-threatening life-threatening conditionconditionneuronal damage, systemic neuronal damage, systemic complicationcomplication

IDIOPATHIC EPILEPSYIDIOPATHIC EPILEPSYMost common cause of seizuresMost 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 setter6 m-5 years (juvenile:8-12w---outgrow by 4-6m)generalizedgeneralized ! ! tonic-clonic seizurestonic-clonic seizures

90% unconsciousness (+psychomotor signs: agression, pacing, hallucination, stargasing, tailchasing)

recur at regular intervalswith aging frequency/severity of seizures NORMAL:physical/neurologic/ophtalmologicclinicopathologic tests/ CSF/ interictal EEGProdromal: aura/preictus-ictus-postictusProdromal: aura/preictus-ictus-postictus

ACQUIRED EPILEPSYACQUIRED EPILEPSY

prior inflamm./traumatic/toxic/metabolic/vascularINSULTINSULT alters a focus of neurons alters a focus of neurons seizureseizure

Usually frontal/temporal lobeUsually frontal/temporal lobeUsually partial! Seizure (no uncosciousness)Usually partial! Seizure (no uncosciousness)

any age/ any breed, either gender dogs/catsany age/ any breed, either gender dogs/catsusually can not be determined the causeusually can not be determined the causeABABNORMAL:NORMAL:physical/neurologic/physical/neurologic/ophtalmophtalmologicalological/clinicopathologic tests/ CSF/clinicopathologic tests/ CSFEEG may be abnormalEEG may be abnormalNo prodromal phase (aura/ictus)No prodromal phase (aura/ictus)Progressive: seizures more frequent/intens/longerProgressive: seizures more frequent/intens/longer

DIAGNOSISDIAGNOSIS

SeizuresSeizures

NationaleNationale Species, breed, age, sexSpecies, breed, age, sex

HistoryHistory/ / DecursusDecursus vaccination, toxin, trauma, drugs, other previous diseases vaccination, toxin, trauma, drugs, other previous diseases seizureseizure: form, type,description (video), onset, duration, : form, type,description (video), onset, duration, frequency, present before, day time, signs between two frequency, present before, day time, signs between two seizureseizureOther complains, clinical signs Other complains, clinical signs

PhysicalPhysical-Ophthalmologi-Ophthalmological-cal-NeurolNeurological examinationogical examinationmm, BCV (temperature, pulse, breathing) mm, BCV (temperature, pulse, breathing) Emergency neurology: consciousness, pupil (size, PLR, Emergency neurology: consciousness, pupil (size, PLR, symmetricy), eye position, nystagmus, motor function symmetricy), eye position, nystagmus, motor function (posture, position of head, ataxia, paresis, reflexes) (posture, position of head, ataxia, paresis, reflexes) cranial reflexes, skull, earcranial reflexes, skull, earRespiratory alterationsRespiratory alterations

Labor examinations (screening test)Labor examinations (screening test)Instrumental examinationsInstrumental examinations

Laboratory test (screening tests)Laboratory test (screening tests)Next the animal: blood glucose!!!! cystocentesisNext the animal: blood glucose!!!! cystocentesisCBCCBC (qualitative, quantitative)

Usually not characteristicUsually not characteristicleucocytosis-inflammatory diseaseleucocytosis left shift-bacterial meningoencephalitislymphopenia-acute viral infectionmicrocytosis with or without thrombocytopenia- PSS

BiochemistryBiochemistryLiver: ALT, GGT, ALP, BA, (NH3), TP, albLiver: ALT, GGT, ALP, BA, (NH3), TP, albKidney: Urea, creatinine, PKidney: Urea, creatinine, PIonogram: Ca, K, Na acid-baseIonogram: Ca, K, Na acid-base

SerologySerologyserologic tests (FeLV/FIV, distemper, toxoplasma)serologic tests (FeLV/FIV, distemper, toxoplasma)

Immunology (?)Immunology (?)IC, ANAIC, ANA

Laboratory testsLaboratory tests

Urinalysis:Urinalysis:-specific gravidity-protein-glucose-ketone-crystalls:

Oxalat: ethylenglycol-toxicosis

ammonium biurate: PSS

Instrumental examinationsInstrumental examinations

CSF (liquor)CSF (liquor)colour, átlátszóságprotein, enzyme activityglucose, electrolytecell numbermicroorganismsContraindikation:coagulopathy, increased ICP

Instrumental Instrumental

USUS:: brain, abdomen brain, abdomen (liver, kidney, pancreas) (liver, kidney, pancreas)

X-RayX-RayEEGEEGCTCTMRMR

TREATMENTTREATMENT

Status epilepticusStatus epilepticusICPICP

STATUS EPILEPTICUS Series of seizures without periods of intervening Series of seizures without periods of intervening consciousness consciousness medical emergencymedical emergency immediate seizure control is immediate seizure control is required!required!seizure>20’ result in permanent neuronal damageseizure>20’ result in permanent neuronal damage

systemic effects of status epilepticus:systemic effects of status epilepticus:-hyperthermia-hyperthermia-lactic acidosis-lactic acidosis-hypoxemia-hypoxemia-cardiac arrythmias-cardiac arrythmias-pulmonary edema-pulmonary edema-death -death

Treatment – in seizing animal in status Treatment – in seizing animal in status epilepticusepilepticus

Iv catheter insertIv catheter insert

Immediately stop ongoing seizuresImmediately stop ongoing seizures DiazepamDiazepam 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 airwayMaintain airway, intubation, oxygen, hyperventilation Pentobarbital-NaPentobarbital-Na (5-15 mg/kg iv. slowly, to effect)

If diazepam not effective repeatedly, or seizure reoccur PropofolPropofol (1-4-(8) mg/kg iv slowly, to effect) Temperature 38-39.5C ICP Blood sampling

Treatment – in seizing animal in status Treatment – in seizing animal in status epilepticusban epilepticusban

Prevent seizure recurrence over following hoursPrevent seizure recurrence over following hours PhenobarbitalPhenobarbital (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 infDiasepam 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 infPentobarbital inf (2-5 mg/kg/h iv slowly, to effect)

Treatment – in seizing animal in status Treatment – in seizing animal in status epilepticusbanepilepticusban

Control refractory seizuresControl refractory seizures PropofolPropofol

Loading dose: 1-3.5 mg/kg to effect Maintenance infusion (0.01-0.25 mg/kg/min 6-24 h

General anesthesiaGeneral anesthesia PropofolPropofol:bolus 4-6 mg/kg →maintain 0.1-0.3 mg/kg/min IsofluranIsofluran Pentobarbital Pentobarbital iv bolus 2-5 mg/kg iv bolus 2-5 mg/kg →maintain 5 mg/kg/h Monitoring:intubation, respiration, ventilation, hypotension

Treatment of CS at homeTreatment of CS at home RectallyRectally diazepam diazepam 1 mg/kg (2. seizure/12-24h) 3-4x repeated 1 mg/kg (2. seizure/12-24h) 3-4x repeated

q 20’. If >2 seizure recur despite this treatment q 20’. If >2 seizure recur despite this treatment →hospital

ICP, cerebral edemaICP, cerebral edema

OXYGENOXYGEN avoid HYPOXEMIA avoid HYPOXEMIA!!PaOPaO22>90 Hgmm Sat>97% PaCO>90 Hgmm Sat>97% PaCO2 2 30-40 Hgmm30-40 Hgmm

Oxygen cage, mask (intranasal/intratracheal NO---may cause Oxygen cage, mask (intranasal/intratracheal NO---may cause sneezing, coughingsneezing, coughingtemporary ICPtemporary ICP))If insufficient oxygenationIf insufficient oxygenation intubation, PP ventillation intubation, PP ventillation

Hypoventilation:Hypoventilation:PaCOPaCO22 (>40 Hgmm) (>40 Hgmm) respiratoric acidosis respiratoric acidosis cranial vasodilatation cranial vasodilatation CBFCBFICPICP

Hyperventilation:Hyperventilation:PaCOPaCO22 (<30 Hgmm) (<30 Hgmm) respiratoric alkalosis respiratoric alkalosis cranial vasoconstriction cranial vasoconstriction CBFCBF cerebral ischemia cerebral ischemia

Short period Short period HYPERVENTILATIONHYPERVENTILATION

ICP, cerebral edemaICP, cerebral edemaFLUID THERAPY!!!!FLUID THERAPY!!!! Tissue perfusion, blood pressure Tissue perfusion, blood pressure

Euvolemia!!! Avoid:overhydration, or restriction Euvolemia!!! Avoid:overhydration, or restriction (hypovol, ischemia)

Isotonic crystalloid, Isotonic crystalloid, colloid, colloid, bloodbloodNo:hypotonic solution (5% Dextrose, 0,45 % NaCl) No:hypotonic solution (5% Dextrose, 0,45 % NaCl)

• IC IC cerebral edemacerebral edema

MANNIT!MANNIT! 0,50,5-1 -1 g/kgg/kg 20’ 20’ 4-8h repeat 1-3x

Not proved that, increase intracranial hemorrhagia Not proved that, increase intracranial hemorrhagia ((more benefit than riskmore benefit than risk)) OOssmotic, „antioxidant”, cerebral motic, „antioxidant”, cerebral microcirculationmicrocirculation

In euvolemIn euvolemiaia !!!!!!(ozm.diuresis(ozm.diuresisintravasc. volumenintravasc. volumen cerebral perfusion cerebral perfusion))

FUROSEMID?? FUROSEMID?? HYPERTONIC SALTSHYPERTONIC SALTS 7,5 % NaCl 4 ml/kg 15’7,5 % NaCl 4 ml/kg 15’

In hypovolemia !!!In hypovolemia !!! (quickly restore the euvolemia)(quickly restore the euvolemia)

ICP, cerebral edemaICP, cerebral edema

CORTICOSTEROID CORTICOSTEROID Not suggestedNot suggested!!May be in brain edema associated tumor???

• MetilprednisolonMetilprednisolon 30 mg/kg iv or DexamethasoneDexamethasone 1 mg/kg iv

ELEVATION ofELEVATION of the HEAD the HEAD 15-3015-30°°avoidance of pressure on the v. jugular

BB11 vitamin 2 mg/kg im ? vitamin 2 mg/kg im ?

ANALGEZIAANALGEZIA in case of traumain case of traumaButorphanol, hydromorphineButorphanol, hydromorphine

Avoid: Avoid: Ketamine/ acepromazine/ xylazineKetamine/ acepromazine/ xylazineInfluance the cerebral blood pressure and the metabolic stageInfluance the cerebral blood pressure and the metabolic stage

Per os antiepileptic treatmentPer os antiepileptic treatmentIf the seizures more frequent than 3-4 /months (4 times/year)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 epilepticusAfter a severe or cluster seizures, status epilepticusSeizure caused by intracranial lesionSeizure caused by intracranial lesionSeizures becoming more frequentSeizures becoming more frequentSevere postictal signsSevere postictal signs

Requirements for antiepileptic drugs:Requirements for antiepileptic drugs:- - effective, without remarkable side effects,effective, without remarkable side effects,- - providing continuous, effective anticonvulsive blood level,providing continuous, effective anticonvulsive blood level,- - practical application (per os/8 hours)practical application (per os/8 hours)

Client educationMonitoring: blood labor

(Ph/Kbr) monitoringLiver function, screening biochemistry

Antiepileptic treatment Antiepileptic treatment Couto 2009Couto 2009 PhenobarbitalPhenobarbital 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 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) if seizure continues: ++ KBrKBr 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 Anticonvulsant treatment Ettinger 2005Ettinger 2005A) KBrA) KBr 40-5040-50 mg/kg mg/kg po 1x

Steady state concentrationSteady state concentration (3 months) 20-2520-25 m mmol/l (2-2,5 mol/l (2-2,5 mmol/l)mmol/l)

If >1 seizure/6-8 week or there is seizure inspite of [Br]=20-25If >1 seizure/6-8 week or there is seizure inspite of [Br]=20-25+ + PhPhenobarbital enobarbital 2,5-4 mg/kg 2x2,5-4 mg/kg 2x

Optimal blood levelOptimal blood level 20-30 mg/ml (20-30 mg/ml ( 86-130 umol/l)86-130 umol/l)

B) B) KBrKBr 60-8060-80 mg/kg po mg/kg po 2x 5 days starter dose (30 mg/kg 4x)2x 5 days starter dose (30 mg/kg 4x) than than 15 mg/kg 2x maintenance dose15 mg/kg 2x maintenance dose

C) If seizure <3-4 week and SE/CS:C) If seizure <3-4 week and SE/CS: KBr 100-300 mg/kg in 4 partsKBr 100-300 mg/kg in 4 parts From next day 40-50 mg/kg 1x From next day 40-50 mg/kg 1x

CATCAT Phenobarbital Phenobarbital 2-2,5 mg/kg 2x2-2,5 mg/kg 2x Diazepam Diazepam 0,5-1 mg/kg 2x 0,5-1 mg/kg 2x

Aim in 5 days 500-800 ng/ml= nmol/lAim in 5 days 500-800 ng/ml= nmol/l

PHENOBARBITAL PHENOBARBITAL 2-5 mg/kg 12h2-5 mg/kg 12hSteady state blood concentration in 10-15 daysSteady state blood concentration in 10-15 daysPeak in 4-(8) hours after oral administration

Therapeutic range: Therapeutic range: (avoid serum separator tube) dogdog: 25-: 25-3535 ug/ml 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 leukopeniaMicrosomal enzyme induction in the liver, (hepatotoxicus) not in cat!

Easy to addict, can not be interrupted quicklyDrugs, inhibit the microsomal enzymes in the liver: (TC, ranitidin, cimetidin, enilkonazol), decrease the liver metabolism of the Ph----[Ph]

KBrKBr Metabolised through the kidney, no hepatotoxicMetabolised through the kidney, no hepatotoxic20-40 mg/kg 20-40 mg/kg (monotherapy)(monotherapy) 15 mg/kg 2x15 mg/kg 2x (add-on drug)(add-on drug)Therapeutic blood level 3 months Therapeutic blood level 3 months [KBr][KBr]

1,5-2.3 mg/ml (15-23 mmol/l) (monotherapy)1,5-2.3 mg/ml (15-23 mmol/l) (monotherapy)1-2 mg/ml (10-20 mmol/l1-2 mg/ml (10-20 mmol/l (together with Ph) (together with Ph)T T 1/21/2=25 days dog T =25 days dog T 1/21/2=11 days cat=11 days cat

Effective as a single agent (monotherapy) Effective as a single agent (monotherapy) Initial drugInitial drug

Ph + KBr Ph + KBr decreasing seizures numberdecreasing seizures numberNot to cats: feline asthma, bronchitisNot to cats: feline asthma, bronchitisBr excretion by kidneys proportional with Cl intake!Br excretion by kidneys proportional with Cl intake!dietary Cl, vagy NaCl infusiondietary Cl, vagy NaCl infusion Br elimination from serum Br elimination from serum Br Br

Adverse effects:Adverse effects:PU/PD, polyphagia, sedation, incoordination, constipationHyperosmol---gastric irritation---vomitus (in more parts,with food)

No A.U.V. form No A.U.V. form (except Crisax),(except Crisax), magistral magistralVery cheep, wide therapic range!Very cheep, wide therapic range!

DIAZEPAMDIAZEPAM DogDog:: - - very short half-lifevery short half-life expensiveexpensive

- status epilepticus - status epilepticus - - its metabolit is alsoits metabolit is also anticonvulsananticonvulsantt, , - tolerance - tolerance to anticonvulsive effect can be developedto anticonvulsive effect can be developed - - blood therapeuticblood therapeutic: 200-500 ng/ml: 200-500 ng/ml - - before/after seizurebefore/after seizure 1-2 mg 1-2 mg rectallyrectally::

sseverityeverity,, risk of risk of status epilepticus status epilepticus -plastic absorbes the drug-plastic absorbes the drug -preictal or aura: 2 mg/kg rectally -preictal or aura: 2 mg/kg rectally

decreases occurrence of CS /SEdecreases occurrence of CS /SE

CatCat:: -- longterm treatment also possible longterm treatment also possible!! - - longer T1/2 longer T1/2 - 2. choice followed Ph- 2. choice followed Ph - optimal blood leveloptimal blood level: : 5500-00-8800 ng/ml00 ng/ml

-idiosyncratic hepatoxicity-idiosyncratic hepatoxicity

FELBAMATEFELBAMATEEffective in Effective in dogs in focal seizuredogs in focal seizure! alone or add-on (PB or KBr)! alone or add-on (PB or KBr)70% urinary excretion than by hepatic metabolism (P450)70% urinary excretion than by hepatic metabolism (P450)15 mg/kg q8h (wide margin safety, can be 15 mg/kg q8h (wide margin safety, can be to 70 mg/kg q8h )to 70 mg/kg q8h )Therapeutic serum level: 25-100 mg/lTherapeutic serum level: 25-100 mg/lDoes not cause sedation Does not cause sedation

ZONISAMIDEZONISAMIDESulfonamide-based, suppresses epileptic foci and blocks the propagation Sulfonamide-based, suppresses epileptic foci and blocks the propagation of epileptic dischargesof epileptic dischargesWell absorbed, hepatically metabolized, long T1/2 (15h)Well absorbed, hepatically metabolized, long T1/2 (15h)alone or add-on Well tolerated with very few side-effectsalone or add-on Well tolerated with very few side-effects5-105-10 mg/kg q12h (if not PB) 10 mg/kg q12h with PB mg/kg q12h (if not PB) 10 mg/kg q12h with PB Therapeutic serum level: 10-40 ug/mlTherapeutic serum level: 10-40 ug/mlVery expensiveVery expensive

LEVETIRACETAMLEVETIRACETAMEffective anticonvulsant in Effective anticonvulsant in dogs and catsdogs and cats! „LEV-binding places”! „LEV-binding places”alone or add-on (PB or KBr)alone or add-on (PB or KBr)Well absorbed, rapidly metabolized, T1/2 (3-4h), excreted unchanged in Well absorbed, rapidly metabolized, T1/2 (3-4h), excreted unchanged in urineurine10-20 mg/kg q8h (wide margin safety)10-20 mg/kg q8h (wide margin safety)expensiveexpensive

GABAPENTINGABAPENTINWell absorbed, renally excreted, T1/2 (3-4h)! (3-4x/day)Well absorbed, renally excreted, T1/2 (3-4h)! (3-4x/day)add-on drug Well tolerated with very few side-effectsadd-on drug Well tolerated with very few side-effects10-2010-20 mg/kg mg/kg q8h q8h (if not PB) ((if not PB) (80 mg/kg q6h)80 mg/kg q6h) Therapeutic serum level: 4-16 mg/lTherapeutic serum level: 4-16 mg/l

CLORAZEPATECLORAZEPATE (Rivotril)(Rivotril)Benzodiazepin (bit more prolonged action than diazepam. Shared Benzodiazepin (bit more prolonged action than diazepam. Shared metabolites with diazepam)metabolites with diazepam)Sole or add-on drug Sole or add-on drug Tolerance can be developed. Withdrawal seizure activityTolerance can be developed. Withdrawal seizure activityAdverse effects: sedation, ataxia, cats: hepatic necrosisAdverse effects: sedation, ataxia, cats: hepatic necrosis1-21-2 mg/kg mg/kg q12h q12h Therapeutic serum level: 300-500 ng/mlTherapeutic serum level: 300-500 ng/ml

PRIMIDONPRIMIDON (not suggested)(not suggested)Phenobarbital + pirimidone/ pirimidone Phenobarbital + pirimidone/ pirimidone alonealonePh Ph by 60 mg by 60 mg / / 250 mg pirimidon 250 mg pirimidonpirimidon: 10 mg/kg 3x (never be the first choice)pirimidon: 10 mg/kg 3x (never be the first choice)Pi------Ph + PEMA (phenylethylmalonamide)Pi------Ph + PEMA (phenylethylmalonamide)Only in dog Only in dog (cat NO)(cat NO)HepatotoxicHepatotoxic

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