MANAGEMENT OF EPILEPSY

PowerPoint Presentation: 

EPILEPSY DR.M.THANGARAJ M.D. D.M., ASSOCIATE PROFESSOR OF NEUROLOGY. Thanjavur medical college, thanjavur

INTRODUCTION: 

INTRODUCTION Incidence and prevalence: 50 Million people have Epilepsy Commonest serious Neurological Condition. Annual incidence in developed countries – 50-70 / 100,000 Developing countries Higher Incidence Varies with age High early childhood Low early adult life Second peak after 65 Year

INTRODUCTION & EPIDEMIOLOGY: 

INTRODUCTION & EPIDEMIOLOGY Known to mankind since EC Effective treatment – 19 th century 1990 – nine new drugs added 70% of seizure controlled by current AED 30% never achieved control

Definitions: 

Definitions Seizure: the clinical manifestation of an abnormal, excessive excitation and synchronization of a population of cortical neurons Epilepsy: recurrent seizures (two or more) which are not provoked by systemic or acute neurologic insults

Semiology of seizure?: 

Semiology of seizure? Clinical semiology starting point of understanding a seizure disorder and making the diagnosis of epilepsy EEG,Video EEG,MRI and Functional imaging helps to lateralizing and localizing seizure focus and syndrome Diagnosis of epilepsy depends upon detailed and accurate history Recording of this chronological sequence of recurrrent,transient,selflimited,involuntary alteration in neurological state i.e., the semiology must be meticulously sought It is the quality of this inquiry allows one to understand the patients complaints and to provide the diagnosis of epilepsy Epilepsy is a clinical diagnosis and no single investigation that can accurately exclude or diagnose epilepsy

ILAE Classification of Seizures : 

ILAE Classification of Seizures SEIZURES PARTIAL GENERALIZED simple partial complex partial secondarily generalized Absence Myoclonic Atonic Tonic Tonic-Cloni c

New Seizure Classification: 

New Seizure Classification ICES to published in 1981 – used by physician as a diagnostic tool Despite some advantage the ICES has limitation, based on clinical and EEG data The semiological classification consists of four major categories – sensorial, consciousness, autonomic and motor Seizure can include symptoms in more than one domain of behavior – so they are classified according to the predominant symptom

Seizure types and characteristics: 

Seizure types and characteristics Seizure type(Generalized) Grand mal Absence Myoclonic Clonic Tonic Atonic Characteristics Unconsciousness, convulsions, muscle rigidity Brief loss of consciouness Sporadic jerking movement Repetitive rhythmic jerking movements Muscle stiffness, rigidity Loss of muscle tone

Seizure types and characteristics continued…: 

Seizure types and characteristics continued… Seizure type(Partial) Simple Partial(awareness is retained) Motor Sensory Autonomic Psychological symptoms Characteristics Jerking, muscle rigidity, head turning Unusual sensation – touch, taste, hearing, vision, smell Stomach sensation Memory or emotional disturbance(Deja vu, fear)

Seizure types and characteristics continued…: 

Seizure types and characteristics continued… Partial complex (impairment of awareness) Partial seizure becomes Generalized seizure Automatism – lip smacking, chewing, walking and repetitive, stereotyped movements Begin as partial and evolves into Grandmal seizure

ILAE developing new classification : 

ILAE developing new classification ILAE will establish four level of classification 1. Descriptive seizure classification based on semiological classification 2. Pathophysiologic seizure classification 3. An Epileptic Syndrome disease classification 4. Classification based on functional disability

Partial Seizures: 

Partial Seizures Simple Partial With somatosensory or special sensory symptoms With motor signs With autonomic symptoms or signs With psychic symptoms

video for Partial motor Seizures: 

video for Partial motor Seizures

Complex Partial Seizures: 

Complex Partial Seizures Impaired consciousness clinical manifestations vary with site of origin and degree of Spread Presence and nature of aura Automatisms Other motor activity Duration typically < 2 minutes Seizures

video for Complex Partial Seizures: 

video for Complex Partial Seizures

Secondarily Generalized Seizures: 

Secondarily Generalized Seizures Begins focally, with or without focal neurological symptoms Variable symmetry, intensity , and duration of tonic (stiffening) and clonic (jerking ) phases Typical duration 1-3 minutes Postictal confusion, somnolence , with or without transient focal deficit

Typical Absence Seizures: 

Typical Absence Seizures Brief staring spells (“petit mal”) with impairment of awareness 3-20 seconds Sudden onset and sudden resolution Often provoked by hyperventilation Onset typically between 4 and 14 years of age Often resolve by 18 years of age Normal development and intelligence EEG: Generalized 3 Hz spike-wave discharges

Video for Absence seizure : 

Video for Absence seizure

EEG: Typical Absence Seizure: 

EEG: Typical Absence Seizure

Atypical Absence Seizures: 

Atypical Absence Seizures Brief staring spells with variably reduced responsiveness 5-30 seconds Gradual (seconds) onset and resolution Generally not provoked by hyperventilation Onset typically after 6 years of age Often in children with global cognitive impairment EEG: Generalized slow spike-wave complexes (<2.5 Hz) Patients often also have Atonic and Tonic seizures

Atypical Absence Seizures: 

Atypical Absence Seizures

Myoclonic Seizures: 

Myoclonic Seizures Epileptic Myoclonus Brief, shock-like jerk of a muscleor group of muscles Differentiate from benign,nonepileptic myoclonus (e.g., whilefalling asleep) EEG: Generalized 4-6 Hzpolyspike-wave discharges

Video for myoclonic seizure: 

Video for myoclonic seizure

Myoclonic Seizures: 

Myoclonic Seizures

Tonic and Atonic Seizures: 

Tonic and Atonic Seizures Tonic seizures Symmetric, tonic muscle contraction of extremities with tonic flexion of waist and neck Duration - 2-20 seconds. EEG – Sudden attenuation with generalized, low voltage fast activity (most common) or generalized polyspike -wave. Atonic seizures Sudden loss of postural tone When severe often results in falls When milder produces head nods or jaw drops. Consciousness usually impaired Duration - usually seconds, rarely more than 1 minute EEG – sudden diffuse attenuation or generalized polyspike -wave

Video for atonic seizure: 

Video for atonic seizure

Tonic and Atonic Seizures: 

Tonic and Atonic Seizures

Generalized Tonic-Clonic Seizures: 

Generalized Tonic- Clonic Seizures Associated with loss of consciousness and post- ictal confusion/lethargy Duration 30-120 seconds Tonic phase Stiffening and fall Often associated with ictal cry Clonic Phase Rhythmic extremity jerking EEG – generalized polyspikes

Video GTCS: 

Video GTCS

Psychogenic Non-epileptic Seizures: 

Psychogenic Non-epileptic Seizures 10-45% of patients referred for intractable spells Females > males Psychiatric mechanism - dissociation, conversion Common association with physical, emotional, or sexual abuse Spells with non-epileptic etiology No obvious ictal eeg correlation (classically normal awake background during episode of impaired consciousness)

Psychogenic Non-epileptic Seizures: 

Psychogenic Non-epileptic Seizures Features Suggestive Of Nonepileptic Psychogenic Seizures Eye Closure Pelvic thrusting Opisthotonus Side-to-side head shaking Prolonged duration (>4 minutes) Stopping and starting Suggestibility

Video for Psychogenic Non-epileptic Seizures: 

Video for Psychogenic Non-epileptic Seizures

Epilepsy cont…: 

Epilepsy cont… The doctor may casually prescribe a AED, but for the patient dreaded confirmation of epilepsy

PowerPoint Presentation: 

Initiation of AED is a major event in the life of epileptic patient Social problem All AED suppress seizure activity Patient has to take AED for long time Exposed to the side effects of AED

KEY WORDS: 

KEY WORDS Single Seizure Does Not Constitute Epilepsy Two Or More Unprovoked Seizure Called Epilepsy 10 Out Of Every 100 Person Have A Single Seizure In Their Life Time AED Therapy Is To Prevent The Recurrence Of Seizure AED Often Associated With Adv Side Effect Administration Is Justified When Benefit More Than Risk

Epilepsy cont…: 

Epilepsy cont… Epilepsy-considered active if patient has had seizure or has been treated with AED in previous 5 years Remission in epilepsy is defined as a period of freedom from seizure expressed for a specific time such as 2,3 or 5 years

WHY SEIZURE TO BE TREATED?: 

WHY SEIZURE TO BE TREATED? Deleterious neuronal plasticity Progressive cognitive decline Psycho-social dysfunction Impaired quality of life Increased morbidity & mortality

PowerPoint Presentation: 

IS IT A SEIZURE? YES ANY PREVIOUS SEIZURES YES RECURRENT SEIZURE (EPILEPSY) FIND REASON FOR RECURRENCE (NON COMPLIANCE, DRUG خ DRAWL, INTRACTABILITY, PROGRESSIVE CNS PATHOLOGY) DETERMINE SEIZURE TYPE(S) INTERNATIONAL CLASSIFICATION CHOOSE AED REGULAR FOLLOW UP CLINICAL ASSESMENT AED LEVELS LFT, CBC NO FIRST SEIZURE HOSPITALISE CT, EEG, CSF Etc ANY CAUSE FOUND? NO IDIOPATHIC NO CONSIDER: SYNCOPE TIA MIGRAINE CEREBRAL TRAUMA NARCOLEPSY TIC DOULOUREUX HYSTERIA MALINGERING YES SYMPTOMATIC RX SP. DISEASE CAUSING SEIZURES WITH OR WITHOUT AED HOSPITALISE(SP.EEG AND INTENSIVE MONITORING AND FNAL IMAGING) ADJUST MEDICATIONS FREQUENT FOLLOW UP

AIM OF TREATMENT: 

AIM OF TREATMENT Complete seizure control Without adverse effect Return to normal life Acceptable control Aim at limiting the number and severity of seizure With a tolerable drug burden Few side effect On option of last resort Seizure freedom ultimate goal

PowerPoint Presentation: 

Newly diagnose epilepsy First drug Second drug Refractory Surgical assessment Rational duotherapy Seizure free Seizure free 47% 13% 40%

TREATMENT OPTIONS: 

TREATMENT OPTIONS Pharmacotherapy Non pharmacological therapy Surgical intervention Ketogenic diet Vagus nerve stimulation

MONOTHERAPY OR POLYTHERAPY WHEN?: 

MONOTHERAPY OR POLYTHERAPY WHEN? Since 1980 mono therapy – gold standard Poly therapy High incidence of drug toxicity Cognitive side effect Drug interaction Without improved outcome Emergence of new AEDs Combination therapy possible Some combination even more successful

PRINCIPLES OF AED TREATMENT: 

PRINCIPLES OF AED TREATMENT Made after discussion of the risks and benefits of treatment. Started with a single conventional AED Start with a low dose,gradually increase until seizures controlled or side effects occur. If initial AED failed or poorly tolerated then use another AED. The dose of second AED gradually increased until adequate or maximum tolerated. If second drug also un helpfull drug with lesser efficacy withdrawn.

Epilepsy cont…: 

Epilepsy cont… Combination therapy can be considered when two AED mono therapy failed. If seizure not controlled patient may be referred to specialist for evolution. Formulation or brand of AED preferably not be changed. Modified release formulations offer ease administration and better compliance

TREATMENT OF FIRST UNPROVOKED SEIZURE: 

TREATMENT OF FIRST UNPROVOKED SEIZURE Epilepsy not diagnosed after single seizure. Risk of second seizure 35-40%. Many individual may not have a second seizure. Risk of third seizure is higher after two unprovoked seizure. Generally first seizure is not treated. The individual and family are explained about risk and recurrance

CIRCUMSTANCES IN WHICH SINGLE SEIZURE MAY BE TREATED: 

CIRCUMSTANCES IN WHICH SINGLE SEIZURE MAY BE TREATED Prolonged focal seizure First seizure presenting as SE Abnormal neurological sign Family history of seizure EEG abnormality Abnormal brain imaging Patient might have had a seizure before but not recognized. High risk jobs. Individual and family do not accept the risk of recurrence

TREATMENT OF NEWLY DIAGNOSED EPILEPSY: 

TREATMENT OF NEWLY DIAGNOSED EPILEPSY AED therapy recommended after two unprovoked seizure. AED therapy started after confirmation of epilepsy. AED treatment differed under following circumstances. Infrequent seizure Occurrence of brief seizure without underlying lesion. BECTS

PowerPoint Presentation: 

SEIZURE TYPE FIRST LINE SECOND LINE/ ADD-ON THIRD LINE / ADD-ON ABSENCE (TYPICAL / ATYPICAL) VPA LTG ESM LEV ZNS MYOCLONIC VPA TPM LEV ZNS LTG CLB CZP PB TONIC –CLONIC VPA CBZ PHT PB* LTG OXC TPM LEV ZNS PRM ATONIC VPA LTG TPM FBM SIMPLE AND COMPLEX PARTIAL WITH OR WITHOUT SECONDARY GENERALISATION CBZ PHT PB* OXC LTG TPM GBP VPA LEV ZNS PGB TGB VGB FBM PRM UNCLASSIFIABLE VPA LTG TPM LEV ZNS CHOICE OF AED IN ADULTS ACCORDING TO SEIZURE TYPE

PowerPoint Presentation: 

DRUG STARTING DOSE(mg/day) COMMONEST DOSE (mg/day) MAINTENANCE DOSE (mg/day) DOSING INTERVAL Carbamazepine 200 600 400-2000 Bd-qds Clobazam 10 20 10-40 Od-bd Clonazepam 1 4 2-8 Od-bd Ethosuximide 500 1000 500-2000 Od-bd Phenobarbital 60 120 60-240 Od-bd Phenytoin 200 300 100-700 Od-bd Primidone 125 500 250-1500 Od-bd Sodium valproate 500 1000 500-3000 Bd-tds DOSING GUIDELINES FOR ESTABLISHED ANTIEPILEPTIC DRUGS IN ADULTS

PowerPoint Presentation: 

DRUG STARTING DOSE (mg/kg/dose) COMMONEST DOSE (mg/day) MAINTENANCE DOSE (mg/kg/dose) DOSING INTERVAL Felbamate 1200 2400 1800-4800 TDS Gabapentin 300-400 2400 1200-4800 TDS Lamotrigine 12.5-25* 200-400 100-800 OD-BD Levetiracetam 1000 2000-3000 1000-4000 BD Oxcarbazepine 150-600 900-1800 900-2700 BD-TDS Pregabalin 150 300 150-600 BD-TDS Tiagabine 4-10 40 20-60 BD-QDS Topiramate 25-50 200-400 100-1000 BD Vigabatrin 500-1000 3000 2000-4000 OD-BD Zonisamide 100 400 400-600 OD-BD DOSE GUIDELINES FOR NEW ANTIEPILEPTIC DRUGS IN ADULTS

PowerPoint Presentation: 

DRUG STARTING DOSE(mg/day) MAINTENANCE DOSE (mg/day) DOSING INTERVAL Carbamazepine 5 10-25 Bd-qds Clobazam 0.25 0.5-1 Od-bd Clonazepam 0.025 0.025-0.1 Bd-tds Ethosuximide 10 15-30 Od-bd Phenobarbital 4 4-8 Od-bd Phenytoin 5 5-15 Od-bd Primidone 10 20-30 Od-bd Sodium valproate 10 15-40 Bd-tds DOSING GUIDELINES FOR ESTABLISHED ANTIEPILEPTIC DRUGS IN CHILDREN

PowerPoint Presentation: 

DRUG STARTING DOSE (mg/kg/dose) MAINTENANCE DOSE (mg/kg/dose) DOSING INTERVAL Felbamate 15 30-45 Tds-qds Gabapentin 20 20-40 Tds Lamotrigine -Monotherapy 0.5 2-8 Od-bd -With valproate 0.15 1-5 Od-bd Levetiracetam 10 20-60 Bd oxcarbazepine 5 10-50 Bd-tds Pregabalin - - - Tiagabine - - - topiramate 0.5-1(od) 5-9 Bd Vigabatrin 40 50-150 Od-bd zonisamide 2-4 4-8 bd DOSE GUIDELINES FOR NEW ANTIEPILEPTIC DRUGS IN CHILDREN

FDA APPROVED MONOTHERAPY: 

FDA APPROVED MONOTHERAPY PRIMARY GENERALISED SEIZURES Ethosuximide Sodium Valproate Phenobarbitone / Primidone Clonazepam Phenytoin

FDA APPROVED MONOTHERAPY: 

FDA APPROVED MONOTHERAPY PARTIAL SEIZURES Carbamazapine Sodium Valproate Phenytoin Lamotrigine Oxcarbazepine

FDA APPROVED MONOTHERAPY: 

FDA APPROVED MONOTHERAPY FDA APPROVED ADJUNCTIVE THERAPY Gabapentin Topiramate Tiagabine Levetiracetam Clorazepate Felbamate

INTRACTABLE EPILEPSY: 

INTRACTABLE EPILEPSY Seizure remained uncontrolled for years despite relevant therapy. Epilepsy with recurrent seizure despite plasma concentration of AED within the therapeutic range

MC NAUGHTON & RASMUSSEN: 

MC NAUGHTON & RASMUSSEN Medical treatment should not be considered intractable unless AED have been used in maximum tolerated doses

DEFINITION CONT…: 

DEFINITION CONT… When seizure control is not achieved with first two appropriate well tolerated AED schedules taken as mono therapy or in combination

CAUSE FOR PSEUDO INTRACTABILITY : 

CAUSE FOR PSEUDO INTRACTABILITY ERROR IN DIAGNOSIS Failure to identify a seizure syndrome or causative factor Incorrect seizure classification NEAD ERROR IN DRUG CHOICE OR MANAGEMENT Wrong drug for the seizure or syndrome Inadequate dosages Inappropriately treating the level POOR MEDICATION/COMPLIANCE Inadequate patient instruction or education Too frequent or complex of dosing schedule Intolerable adverse effect of medication TRUE PHARMACOLOGICAL INTRACTABILITY

PowerPoint Presentation: 

FEATURES OF MEDICALLY INTRACTABLE SEIZURES Etiologies MTS, TS, SWS, Cerebral tumors, hamartoma , AVMs, developmental malformations, and sequelae of cerebral infections, infarcts or trauma Catastrophic epilepsies West syndrome, Lennox- Gastaut syndrome, progressive myoclonic epilepsy and cerebral metabolic disorders Common seizure types Complex partial, tonic, atonic, and atypical absence Common clinical features Mental retardation, focal neurologic deficits, and concurrent psychiatric illness

REFRACTORY EPILEPSY PROGRESSIVE OR DENOVO: 

REFRACTORY EPILEPSY PROGRESSIVE OR DENOVO Drug resistant? - Primary or repeated seizure Seizure beget seizure - GOWER’s 19 th century Reinforced by RODIN 1960 Long h/o, high no. of pre treatment seizure, poor outcome Early treatment prevent drug resistance

MECHANISM OF DRUG RESISTANCE: 

MECHANISM OF DRUG RESISTANCE Repeated seizure  neuronal loss, mossy fibre sprouting in hippocampus More seizure following excitatory recurrent circuits MRI  smaller hippocampal volume ipsilateral to seizure focus

CAUSES OF DRUG RESISTANCE: 

CAUSES OF DRUG RESISTANCE Repeated seizure  neuronal loss, mossy fibre sprouting in hippocampus More seizure following excitatory recurrent circuits MRI  smaller hippocampal volume ipsilateral to seizure focus

CAUSES OF DRUG RESISTANCE: 

CAUSES OF DRUG RESISTANCE Epileptogenesis – knowledge incomplete Few well defined epileptic syndrome has clear genetic basis – refractory epilepsy Altered ion channel structure Hyperexcitability and hypersynchronised discharge of large no. of neurons Ontogenic abnormalities in brain maturation Alteration in neuronal network Kindling phenomenon Glial properties in seizure prone area

DRUG TRANSPORTER PROTEINS: 

DRUG TRANSPORTER PROTEINS Pharmaco resistance epilepsy – resistant to many AEDS ? Common mechanism Recent theory – multi drug transporter protein ATP dependent efflux protein Include p – Glycoprotein (PGP) and multi drug resistant associated protein (MRP) Increased expression of MDR1 gene – identified in surgically resected tissue from patients with IE Increased expression of PGP and MRP1 push AED from the site of origin of seizure – Inadequate intracellular concentration of AED

WHEN IS EPILEPSY INTRACTABLE: 

WHEN IS EPILEPSY INTRACTABLE How long should one preserve with AED before diagnosing pharmaco RE How many regimens should we try Should combination tried early? which one Are some combination better than others? For which patient? How to predict intractability?

Combination of drugs reported to be useful in refractory epilepsy: 

Combination of drugs reported to be useful in refractory epilepsy Combination Indication Sodium Valproate & Ethosuximide Generalised absence Carbamazepine & Sod. Valproate Complex partial seizures Sod. Val And Lamotrigine Partial/gen. seizures Topiramate & Lamotrigine Partial / generalised Vigabatrin & Lamotrigine Partial Vigabatrin & Tiagabine Partial

KETOGENIC DIET: 

KETOGENIC DIET High fat Low protein Very low carbohydrate Given to children under 5 – 10 yrs with IE Less experience in adoloscent and adult Mimics biochemical changes like starvation Creates ketosis Exact mechanism unclear RESTRICTIVE DIET

PowerPoint Presentation: 

Ketogenic diet contd…… First developed 1920 Out of favor due to AED Reinforced in 1990 Very effective in IE Does not have cumulative side effect

INITIATION AND ADMINISTRATION: 

INITIATION AND ADMINISTRATION Ratio of fat to carb and protein 2:1 to 4:1 Patient must be admitted for several days To monitor hypoglycemia To educate the patient and family

CONT… EFFICACY AND TOLERABILITY: 

CONT… EFFICACY AND TOLERABILITY 50% seizure reduction after 1 year Effective in all seizure Dehydration, diarrhoea, hypoglycemia, wt. Loss, acidosis – side effect Hyperlipedimia and renal stone less common Rarely Dialated Cardiomyopathy and prolonged QT interval

A TYPICAL DAYS MEAL FOR A CHILD ON A KETOGENIC DIET: 

A TYPICAL DAYS MEAL FOR A CHILD ON A KETOGENIC DIET Breakfast Lunch Dinner 60g 36% heavy cream 60g 36% heavy cream 60g 36% heavy cream 20g fruit 35g vegetables 24g vegetables 39g eggs 19g white tuna fish 31g beef hot dog 22g butter 24g butter or margarine 14g butter or margarine 40g sugar free gelatin

VAGAL NERVE STIMULATION: 

VAGAL NERVE STIMULATION New non pharmacological treatment >20,000 patients receiving treatment Approved in USA, CANADA and EUROPE As adjunctive therapy for partial onset RS in adults and adolescents and some with Gen. Seizure

PowerPoint Presentation: 

VNS SYSTEM HAND HELD MAGNET PROG WAND PROG SIGNAL GENERATOR BIPOLAR LEAD LEFT VAGUS

PowerPoint Presentation: 

VNS cont… Mechanism of action unknown No effect on hepatic or serum concentration of AED Does not have deleterious effect on cardiac or pulmonary function

EFFICACY & TOLERABILITY: 

EFFICACY & TOLERABILITY IE Patient treated with VNS 1/3 rd – 50% Seizure reduction 1/3 rd - <50% seizure reduction 1/3 rd – no improvement Few become seizure free Considered equally efficacious as the addition of 2 nd or 3 rd AED

SIDE EFFECTS: 

SIDE EFFECTS Transient Voice alteration Chest discomfort Hoarseness Throat pain

EPILEPTIC SURGERY: 

EPILEPTIC SURGERY Often under used Compliment to medical treatment in refractory cases Ideally selected patients have 58% seizure free at 1yr compared with 8% of medically treated patients

TYPE OF EPIPLEPSY SURGERY AND THEIR INDICATIONS: 

TYPE OF EPIPLEPSY SURGERY AND THEIR INDICATIONS PROCEDURE INDICATION Anterior temporal lobectomy Mesial temporal sclerosis Focal resection Partial onset seizures arising from resectable cortex Corpus callostomy Tonic, atonic or tonic- clonic seiures with falling and injury: large non- resectable lesions: secondary bilateral synchrony Hemispherectomy Rasmussen’s syndrome or other unilateral hemisphere pathology in association with functionally impaired contralateral hand Subpial transections Partial onset seizures arising from unresectable cortex

PRESURGICAL EVALUATION: 

PRESURGICAL EVALUATION Aims to establish drug resistance To delineate the epileptogenic zone to be resected Review of patient seizure h/o and AED trial Sophisticated video EEG monitoring High quality MRI PET and SPECT Study Neuro psychological testing WADA test

OTHER MEASURES: 

OTHER MEASURES Cerebellar stimulation Deep brain stimulation Gamma knife surgery Calcium and Vit-D supplements

ROLE OF NEWER AEDS: 

ROLE OF NEWER AEDS Recommended for those who not benefited from conventional AED. New AED are as effective as the conventional drugs. Little costlier. Newer AED are used when contraindication to first line drugs due to co-existing illnesses. The first line drugs interact with other drugs like OC,anti-coagulants.

DRUG INTERACTIONS: 

DRUG INTERACTIONS Many interaction between different AEDs and other drugs that the patient taking. Detailed knowledge of pharmaco kinetics of AEDs and other drugs is necessary. Certain AEDs(PHT,PB,CBZ,OXC) induce hepatic enzymes. VPA inhibit hepatic enzymes and slows the metabolism of concomitant AEDs causing toxicity. Drug interaction become important while using AEDs with Theophyline group Erythromycine Ciprofloxacin ATT Anti retro viral drugs

WHEN TO WITHDRAW AEDS: 

WHEN TO WITHDRAW AEDS Withdraw in most cases after a seizure free period of two to three years. Decision is mainly based on type epilepsy syndrome and cause of seizures. Taken after discussion of risks and benefits of withdrawal . AED withdrawl should be avoided in certain epilepsy syndromes eg.JME,LGS etc.

WHEN TO WITHDRAW AEDS: 

WHEN TO WITHDRAW AEDS AEDs are usually withdrawn gradually over atleast 3 to 6 months. The tapering of dose may be performed at a slower rate for benzodiazepines. Withdraw one drug at a time those who are on multiple AED. If seizure recurs during or after AED withdrawl the person advised to revert to their AED dose before.

WHEN TO REFERRED BACK TO THE EPILEPSY SPECIALIST: 

WHEN TO REFERRED BACK TO THE EPILEPSY SPECIALIST Unresponsive to treatment with the first two AED schedules Having Significant side effects with treatment Planning a pregnancy Considering withdrawal of therapy

PowerPoint Presentation: 

PROGNOSIS Majority have a good prognosis Strongly influenced by underlying cause Many people – Particularly children will remit Substantial proportion have epilepsy all their lives 30-40% have seizure FACTORS INDICATE POOR PROGNOSIS Symptomatic epilepsy High seizure frequency before AED GTCS Gen Epileptiform activity on EEG Family H/O epilepsy Co. Morbid psychiatric history

PowerPoint Presentation: 

MORTALITY : 2 to 3 times above the general population Many Cause of death related to underlying etiology SUDEP 17 % all epilepsy related deaths

PowerPoint Presentation: 

SUDEP sudden / unexpected / witnessed or un witnessed, non traumatic , non drowning death in patients with epilepsy. Incidence : 0.35 to 10 /1000 per patients / year Higher incidence if seizure remains uncontrolled. OTHER CAUSE OF DEATH: Drowning Burns Aspiration Pneumonia, SE Sucide

ROUTINE LABORATORY TESTS DURING AED THERAPY : 

ROUTINE LABORATORY TESTS DURING AED THERAPY Complete blood count, LFT,RFT Serum calcium, alkaline phosphatase and other tests for bone metabolism Minor abnormalities are not an indication for change in medication.

STATUS EPILEPTICUS : 

STATUS EPILEPTICUS Common medical emergency Associated with high morbidity if not mortality Mortality from SE 3 to 50% RSE in elderly death more than 76% Life time prevalence SE in PWE 1 to 16 %

PowerPoint Presentation: 

DEFINITION FOR SE Seizure lasting more then 30 mints or occurrence of two or more seizure without recovery of consciousness in between LOWENSTEIN ET AL Continues generalized convulsive seizure lasting more then 5 mints or two or more seizure during which patient does not return to base line consciousness Any seizure that last more then 2 minis dissevers to be managed SE

PowerPoint Presentation: 

REFRACTORY STATUS E EPILEPTICUS Continues or repetitive seizure lasting longer than 60 minis despite treatment with benzo diazepine and another standard anticonvulsant (PHT) in adequate dose MALIGNANT SE Is a severe variant of RSE, in which the seizure fails to response to treatment with even anesthetic agent

CLASSIFICATION OF SE : 

CLASSIFICATION OF SE Convulsive SE - tonic - clonic - Tonic - Clonic - Myoclonic Non convulsive SE - generalized electrical seizure lasting for atlest 30 min but without physical convulsion

NCSE: 

NCSE CSE may evolve into NCSE Characterized by Abnormal mental status UN responsiveness Occurlar motor abnormalities Persistent electro graphic seizure Possible response to anticonvulsant Absence status CPSE –rare

MANAGEMENT OF CONVULSIVE SE: 

MANAGEMENT OF CONVULSIVE SE AT CLINIC OR OUTSIDE HOSPITAL Maintain airway and assess cardio – respiratory function Brief history and examination Inject rectal diazepam – 10 mg (adults) or 0.5 mg / kg (children) Or Give buccal midazolam 10 mg (adults) or 0.2 mg / kg (children ) If seizure persist , shift the patient to the nearest hospital

SE Treatment Algorithm: 

SE Treatment Algorithm One commonly used treatment algorithm is: First 5 minutes : Check emergency ABC’s Give O2 Obtain IV access Begin EKG monitoring Check fingerstick glucose Draw blood for Chem-7, Magnesium, Calcium, Phosphate, CBC, LFTs, AED levels, ABG,Troponin Toxicology screen (urine and blood).

SE TREATMENT Cont…: 

SE TREATMENT Cont… 6-10 minutes Thiamine 100 mg IV; 50 ml of D50% IV unlessadequate glucose known. Lorazepam 4 mg IV over 2 mins ; if still seizing, repeat X 1 in 5 mins. If no rapid IV access give diazepam 20 mg PR or midazolam 10 mg intranasally , buccally or IM.

SE TREATMENT Cont…: 

SE TREATMENT Cont… 10-20 minutes If seizures persist, begin fosphenytoin 20 mg/kg IV at 150 mg/min, with blood pressure and EKG monitoring. Reasonable to bypass this step, or perform subsequent step simultaneous with fosphenytoin loading

SE Treatment Algorithm: 

SE Treatment Algorithm 10-60 minutes: one (or more) of the following 4 options: (intubation usually necessary except for valproate ) Continuous IV midazolam : Load: 0.2 mg/kg; repeat 0.2-0.4 mg/kg boluses every 5 minutes until seizures stop, up to a maximum total loading dose of 2 mg/kg. Initial rate: 0.1 mg/kg/hr. cIV dose range: 0.05 – 2.9 mg/kg/hr. OR Continuous IV propofol : Load: 1 mg/kg; repeat 1-2 mg/kg boluses every 3-5 minutes until seizures stop, up to maximum total loading dose of 10 mg/kg. Initial cIV rate: 2 mg/kg/h. cIV dose range: 1-15 mg/kg/hr. Avoid >48 hrs of >5 mg/kg/h (increased risk of propofol infusion syndrome). OR IV valproate : 40 mg/kg over ~10 minutes. If still seizing, additional 20 mg/kg over ~5 minutes. OR IV phenobarbital: 20 mg/kg IV at 50-100 mg/min.

SE Treatment Algorithm: 

SE Treatment Algorithm 60 minutes: Continous IV Pentobarbital. Load: 5 mg/kg at up to 50 mg/min; repeat 5 mg/kg boluses until seizures stop. Initial cIV rate: 1 mg/kg/hr. cIV -dose range: 0.5-10 mg/kg/hr; traditionally titrated to suppression-burst on EEG. Begin EEG monitoring if patient does not rapidly awaken, or if any CIV treatment is used. ~20% of those patients successfully treated clinical for status will still be seizing on EEG.

MANAGEMENT OF RSE: 

MANAGEMENT OF RSE Anesthetic agent: Adults and children – midazolam 0.2 mg / kg IV (maximum 10 mg) bolus over 2 min followed by 0.1 – 0.4 per kg per hour continuous IV in infusion. Propofol 2- 5 mg per kg IV bolus followed by 5- 10 mg per kg per hour IV infusion. Thiopental 10 -20 mg per kg IV bolus followed 0.5 -1 mg per kg per hour IV infusion.

RSE cont…: 

RSE cont… Coma phase - continue pharmacologic coma for 12 hours after last seizure EEG – burst suppression Weaning phase - reduce infusion of Anesthetic agent ever 3 hour with EEG monitoring General measure – management hyperthermia, acidosis and hemodynamic instability

FOLLOWING SE CONTROL : 

FOLLOWING SE CONTROL Maintenance AED therapy to prevent recurrence seizure Known epileptic – usual AED maintained and dose adjustment may required First time SE drug like PHT or VPA can be continued as oral NCSE may not require long term AED. When required choose depending upon clinical seizure

WOMEN WITH EPILEPSY: 

WOMEN WITH EPILEPSY WWE who are in the reproductive age group ideally evolutes by a specialist. WWE who continue appropriate AEDs have more than 90% chance of having a normal pregnancy and children.

CONTRACEPTION: 

CONTRACEPTION Doctor should keep in mind possibility of marriage and pregnancy in all WWE who are in reproductive age group. Issues related to epilepsy and use of AED and its drug interaction with OC should be discussed. All WWE should be advised to plan their pregnancies. Cautioned that some AEDs may make the OC ineffective. Depot injections of progesterone and OC with high dose estrogen preferred.

PRECONCEPTION COUNSELLING: 

PRECONCEPTION COUNSELLING All WWE in reproductive age group need preconception counseling. Responsibility of doctor-to alleviate the fear about pregnancy and delivery. All WWE in reproductive should be started on folic acid 5mg/day.

Cont…: 

Cont… Risk of major fetal malformation is approximately 5% higher among children born to WWE who are exposed to AED. Risk is further reduced when the mother is using mono therapy along with folic acid. Seizure may remain in 50% of WWE or improve (25% )or even worsen (25%) during pregnancy. Whenever possible women should receive lowest effective dose of AED.

PREGNANCY: 

PREGNANCY AEDs should be continued in pregnancy. Abrupt discontinuation of AED leads to breakthrough seizure. Pregnancy in WWE should be jointly managed by obstetrician and physician attending the patient. All WWE folic acid 5mg daily if not previously started. Folic acid needs to be continued until delivery . Seizure frequency should be monitored carefully and AED doses adjusted to minimize the number of seizures. Serum level of AEDs are helpful during pregnancy.

PREGNANCY CONT…......: 

PREGNANCY CONT…...... All pregnant WWE should be advised screening for fetal malformation by serum alpha feto protein at sixteen weeks and by detailed USG at 18 weeks. All WWE should be given two doses of vitamin k-10mg of IM at 34 and 36 weeks of pregnancy. All infants born to mother taking AED should be given vitamin k-1 mg IM at birth.

LABOUR: 

LABOUR WWE should have the delivery in hospital under super vision of gynecologists who have access to specialists. There should be facility for cesarean section and neonatal critical care. Factors predisposing to seizures in labour (fear, pain,sleep deprivation, hypoglycemia). There is no contraindication for spinal/epidural anesthesia.

Cont…: 

Cont… Use of oral AED should be continued during labour and post partum. Women unable to tolerate oral medications,AED can be given parenteral route. An elective caesarean section should be considered if there have been a frequent seizure towards the end of pregnancy. Seizure during labour should be terminated by IV Lorazepam or Diazepam. If seizure recur other etiological possibilities-CVT,Eclampsia etc should be considered.

PowerPoint Presentation: 

IN HOSPITAL SETTING Maintain airways and assess cardio – respiratory function Take brief history and perform physical and neurological examination Take blood sample for glucose, urea, AED level and other as appropriate Inject PHT : 15 -20 mg / kg IV at maximam rate of 50 mg /min or equivalent dose of fosphenytoin ( if available ) Perform CT scan, lumbar puncture if indicated Consult neurologist if seizure persist If seizure still continue patient should be shifted to a specialized center capable of dealing with refractory status epilepticus and having ventilation and ICU facilities

ELEMENTS OF SUCCESSFUL TREATMENT : 

ELEMENTS OF SUCCESSFUL TREATMENT Classify the seizure disorder correctly Maximize mono over poly therapy Balance the maximal effective dose with minimal side effects Choose dosing to maximize compliance Treat the patient’s symptoms, not the EEG or the serum levels Patient and family education regarding epilepsy is essential Ideal antiepileptic drug not only fit for fit but also fit for the patient

PowerPoint Presentation: 

Thank you