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This document discusses seizures and epilepsy in children. It defines a seizure as abnormal excessive neuronal activity in the brain and epilepsy as two or more unprovoked seizures occurring more than 24 hours apart. Seizures can be focal, originating in one area of the brain, or generalized, involving both hemispheres simultaneously. Epilepsy syndromes are described. Imaging and EEG play roles in evaluating seizures, with MRI being preferred and EEG showing localized or generalized abnormalities.

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• Dr.C.S.N.Vittal Seizure Disorders in Children
Seizure (Latin sacire, “to take possession of”) A transient occurrence of signs and/or symptoms resulting from abnormal excessive or synchronous neuronal activity in the brain.
Epilepsy Epilepsy is a disorder characterized by two or more unprovoked seizures occurring more than 24 hours apart beyond neonatal period.
• A seizure is the event Seizure vs Epilepsy • Epilepsy is the disease associated with spontaneously recurring seizures
Convulsion A convulsion is any seizure (not necessarily epileptic) characterized by excessive, abnormal muscle contractions, which are usually bilateral.
Epilepsy – new definition Epilepsy is a disease of the brain defined by any of the following: 1. A least two unprovoked (or reflex) seizures occurring >24 h apart 2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years 3. Diagnosis of an epilepsy syndrome • Robert S fisher et al; A practical clinical definition of epilepsy: Epilepsia, 55($):475-482, 2014
Risk of epilepsy after 2 seizures • Hauser et al. Risk of recurrent seizures after two unprovoked seizures. NEJM 1998;338:429.
Seizures Focal The first clinical and electroencephalographic (EEG) changes suggest initial activation of a system of neurons limited to part of one cerebral hemisphere The first clinical and EEG changes indicate synchronous involvement of all of both hemispheres Generalized
Some terminology • Dr Neeta Naik, Guidelines for Diagnosis and Management of Childhood Epilepsy; Expert Committee On Pediatric Epilepsy, IAP; Ind Ped, Vol 46 Aug 17, 2009: 681-698
Some terminology
Epilepsia Partialis Continua
Status Epilepsy (>100 / 100000 population) • Recurrent epileptic seizures continuing for more than 30 minutes without full recovery of consciousness before the next seizure begins, or continu- ous clinical and/or electrical seizure activity lasting for more than 30 minutes whether or not consciousness is impaired’ Clinical Definition New Operational Definition (children > 5 yrs) • “Greater than or equal to 5 minutes of continuous seizures or two or more discrete seizures between which there is incomplete recovery of consciousness.” • A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Eugen Trinka, et al; Epilepsia, 56(10):1515–1523, 2015 doi: 10.1111/epi.13121
Time definition for CSE for treatment purposes (Operational definition) Key time periods in natural history of seizure 0 5 15 30 Interval within which most seizures spontaneously stop Optimum interval for initiation of rescue therapy Time definition for CSE for epidemiological, pathophysiological and outcome purposes
Status Epilepsy - ILAE A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Eugen Trinka, et al; Epilepsia, 56(10):1515–1523, 2015 doi: 10.1111/epi.13121 Tonic-Clonic Focal with impaired consciousness Absences Point 1 (t1) the earliest time when treatment should be started. 5 min 10-15 min 15 min Point 2 (t2) when long-term consequences, such as neuronal injury, neuronal death 30 min > 60 min Unknown
Convulsive Status epilepticus Complex partial, absence, myoclonic status, epilepsia partialis continua, and neonatal status epilepticus, confusional state, hyperactivity with behavioral problems, fluctuating impairment of consciousness with at times unsteady sitting or walking, fluctuating mental status, confusional state, hallucinations, paranoia, aggressiveness catatonia, and or psychotic symptoms. Non-convulsive Status epilepticus Status Epilepticus Generalized tonic, clonic, or tonic–clonic
Mechanisms which Underlie Seizure Generation • Abnormalities at the cell membrane level (ion channels and receptors) and in neuronal circuits • 3 main classes of voltage gated ion channels have been described: Na+, Ca2+, K+. • Sodium currents are involved in the generation of action potentials. • Potassium currents cause hyperpolarization and hence stabilize the neuronal membrane. • Both calcium and sodium currents are involved in the generation of burst discharges, generated by certain classes of neurones when excited. • Gamma amino butyric acid (GABA) and glycine are inhibitory neurotransmitters while glutamate and aspartate are excitatory neurotransmitters. • A useful, though simplistic model of epilepsy is that it involves an imbalance of excitatory and inhibitory neurotransmitter systems within the CNS.
Mechanisms which Underlie Seizure Generation 2. Involves an imbalance of excitatory (glutamate and aspartate) and inhibitory (Gamma amino butyric acid and glycine ) neurotransmitter systems within the CNS. 1. Abnormalities at the cell membrane level (ion channels and receptors) and in neuronal circuits
The 2017 ILAE Classification of Seizures Robert S. Fisher, MD, PhD Maslah Saul MD Professor of Neurology Director, Stanford Epilepsy Center In 2017, the ILAE released a new classification of seizure types, largely based upon the existing classification formulated in 1981.
Motor Tonic-clonic Other motor Non-Motor (Absence) Unknown Onset Motor Non-Motor focal to bilateral tonic-clonic Generalized Onset Focal Onset Motor Tonic-clonic Other motor Non-Motor ILAE 2017 Classification of Seizure Types Basic Version 1 Unclassified 2 Aware Impaired Awareness From Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia doi: 10.1111/epi.13671 1 Definitions, other seizure types and descriptors are listed in the accompanying paper & glossary of terms 2 Due to inadequate information or inability to place in other categories
Motor tonic-clonic clonic tonic myoclonic myoclonic-tonic-clonic myoclonic-atonic atonic epileptic spasms2 Non-Motor (absence) typical atypical myoclonic eyelid myoclonia Unknown Onset Motor Onset automatisms atonic2 clonic epileptic spasms2 hyperkinetic myoclonic tonic Non-Motor Onset autonomic behavior arrest cognitive emotional sensory focal to bilateral tonic-clonic Generalized Onset Focal Onset Aware Impaired Awareness Motor tonic-clonic epileptic spasms Non-Motor behavior arrest ILAE 2017 Classification of Seizure Types Expanded Version Unclassified3 2 These could be focal or generalized, with or without alteration of awareness 3 Due to inadequate information or inability to place in other categories From Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia doi: 10.1111/epi.13671
focal onset aware impaired awareness motor onset (seizures with physical movement) automatisms atonic clonic epileptic spasms hyperkinetic myoclonic tonic non-motor onset (seizures without physical movement) autonomic behaviour arrest congnitive emotional sensory motor onset (seizures with physical movement) automatisms atonic clonic epileptic spasms hyperkinetic myoclonic tonic non-motor onset (seizures without physical movement) autonomic behaviour arrest congnitive emotional sensory focal to bilateral tonic clonic seizure (sec generalized seizures) seizures start in, and affect one part of the brain focal aware seizures (simple partial seizures) focal impaired awareness seizures (complex partial seizures)
generalized onset seizures start in, and affect both sides of the brain at once and happen without warning motor (with physical movement) non-motor (absence) (without any physical movement) Motor tonic-clonic clonic tonic myoclonic myoclonic-tonic-clonic myoclonic-atonic atonic epileptic spasms2 Non-Motor (absence) typical (3 Hz spike & slow wave ) atypical (1-2 Hz spike & slow wave with head atonia and myoclonus) myoclonic eyelid myoclonia
unknown onset (cryptogenic epilepsy) unclassified motor (with physical movement) non-motor (without any physical movement) if doctors are not sure where in the brain the seizure starts If there is not enough information available about the person’s seizure or because of the nature of the seizure.
Etiology of Seizures – Neonatal Period • Birth asphyxia or trauma • Intracranial hemorrhage • Hypoglycemia • Hypocalcaemia or hypomagnesemia • Infections: meningitis, septicemia, tetanus neonatorum • Inborne errors of metabolism • Pyridoxin dependent seizures • Maternal withdrawal of medications • Accidental injection of local
Text Text Etiology of Seizures – Beyond Neonatal Period • Vascular: hemorrhage , AV malformations, intracranial thrombosis • Cerebral malformation: neurocutaneous syndromes, neuronal migration disorders • Drugs/Poisons: Phenothiazines, lead salicylates, phenytoin, CO, strychnine • Miscellaneous: Hypertensive encephalopathy, gray matter degeneration, storage disorders • Simple febrile convulsions • Epilepsy syndromes • Infections: meningitis, encephalitis, Reye syndrome, cerebral malaria • Metabolic causes: Dyselectrolytemia, hypocalcemiam hypomagnesemia, IEM • Space occupying lesions: Neoplasm, brain abscess, tuberculoma, cysticercosis • Trauma:
Febrile Seizures FS is a seizure occurring in childhood after one month of age, associated with a febrile illness that is not caused by an infection of the central nervous system ILAE Definition: Febrile seizures are seizures that occur between the ages of 6 and 60 mo (peak 12-18 mo) with a temperature of 38°C (100.4°F) or higher, that are not the result of CNS infection or any metabolic imbalance, and that occur in the absence of a history of prior afebrile seizures Nelson Text Book Definition:
Febrile Seizures – Types Simple • Primary generalized, • usually tonic–clonic, • attack associated with fever • Lasting for a maximum of 15 min • Do not recurrent within a 24- hr period • Do not have an increased risk of mortality Complex • Focal • Prolonged (>15 min) • Recurs within 24 hours • 2-fold long-term increase in mortality rates, as compared with the general population, over the subsequent 2 yr, probably sec to a coexisting pathology
Febrile status epilepticus … is defined as one lasting over 30 minutes. Febrile seizure plus When the febrile seizures continue after age 5 or other types of seizure develop. FS+ usually end in early adolescence. ... • Febrile infection–related epilepsy (FIRES): In children >5 yr) usually male children and associated with an encephalitis-like illness but without an identifiable infectious agent. Children with FIRES were previously normal but subsequently develop difficult-to-treat epilepsy. • Generalised epilepsy with febrile seizures plus (GEFS+): Children may go on to have febrile seizures well beyond 6 yrs age, even into adult life. They may also develop other seizure types not associated with a high temperature. An epileptic syndrome.
Risk factors for Recurrence No risk factors 12% 1 risk factor 25-50% 2 risk factors 50-59% 3 or more risk factors 73-100% Febrile Seizures – Risk Factors MAJOR • Age < 1 yr • Duration of fever < 24 hr • Fever > 38-390C (100.4 – 102.20F) MINOR • Family history of febrile seizure • Family history of epilepsy • Complex febrile seizure • Daycare • Male gender • Lower serum sodium at time of presentation • Nelson Textbook of Pediatrics, 21E
Epilepsy Syndromes Male, 2-13 yrs Mostly nocturnal Motor & somatosensory – older children Hemiclonic / GTCS – younger children Most AEDs effective, Recovery before 15-16 yrs Commonest generalized epilepsy in 5-16 yrs olds GTCSs 3-6 Hz generalized polyspikes and waves in EEG Improve after 4th decade 3-10 %, Genetic pre disposistion Male preponderance, Onset 1-8 yrs Poor prognosis Hypsarrhythmia , Tuberous sclerosis Typically in 3-5 yrs age group Severe, Complex epilepsy Multiple concurrent seizure types Cognitive dysfunction Benign Rolandic Epilepsy Juvenile Myoclonic Epilepsy West Syndrome (Infantile Spasms) Lenox Gestaut Syndrome
Benign epilepsy with occipital spikes • headaches that occur independently or postictally (epilepsy–migraine sequence) Panayiotopoulos type •Occur in early childhood •Manifests with focal seizures •Impaired awareness •Ictal vomiting Gastaut type •appear in later childhood •focal seizures with •impaired awareness •Visual auras, and •migraine
Seizure Evaluation on First Visit 1 Seizure / seizure mimic ? 2 Is it unprovoked / provoked seizure? 3 Generalized / focal seizure? 4 Etiology? 5 Any associated comorbidities? 6 Treatment received till now?
Role of Imaging • MRI is the imaging modality of choice! But not urgent • Significant cognitive or motor impairment of unknown etiology • Unexplained abnormalities on neurologic examination • Focal seizure with or without secondary generalization • EEG that does not represent a benign partial epilepsy or primary generalized epilepsy • Seizure in children under 1 year of age • If MRI can not be done, better don’t do imaging!! - Epilepsia, 50(9): 2147-2153, 2009
Quietly sitting, relaxed, eyes closed 20-60 mV Most common waves. During mental thought & activity 2-20 mV 20-100 mV Common in children. Displeasure, pleasure, and drowsiness Very irregular &slow waves. Deep sleep in most people 20-200 mV Gamma ( g ) 36-44 Hz 3-5 mV With sudden sensory stimuli
Role of EEG • EEG when abnormal can suggest the nature of the seizure tendency as focal or generalized, but does not determine whether or not a spell was a seizure or whether or not to treat,. • 50% of patients with partial seizures show focal spikes (or slowing), up to 75% after repeat studies or sleep deprivation. • 90% of patients with generalized seizures show generalized spikes, more with sleep deprivation, hyperventilation, or photic stimulation. • A normal EEG would favor partial onset seizures in a patient with epilepsy. • 1-2% of nonepileptics have spikes on their EEGs. • 20% of patients with spikes on the EEG do not have epilepsy.
Role of EEG in Office practice Supports the clinical diagnosis of epilepsy 1 To classify epilepsy : Focal vs Generalized epilepsy 2 To identify epilepsy syndromes 3 3 To predict recurrence risk and to prognosticate 4 4 Unexplained GDD/worsening/autistic regression 5 • K.M.Pearce, H.R. Cock, Seizure 2006
A. Onset of a tonic seizure showing generalized repetitive sharp activity with synchronous onset over both hemispheres. B. Burst of repetitive spikes occurring with sudden onset in the right temporal region during a clinical spell characterized by transient impairment of external awareness. C. Generalized 3-Hz spike-wave activity occurring synchronously over both hemispheres during an absence (petit mal) attack. Horizontal calibration: • MJ Aminoff [ed]: Aminoff’s Electrodiagnosis in Clinical Neurology, 6th ed. Oxford, Elsevier Saunders, 2012.)
EEG interpretation – in general Finding Likely Diagnosis Spike followed by slow waves Interictal pattern of epilepsy 3 Hz spike and wave discharges; provoked by hyperventilation Absence epilepsy Chaotic high voltage of poyspikes with photosensitivity West syndrome Spike wave complexes in Rolandic areas Juvenile myoclonic epilepsy Brief bursts of polyspikes with photosensitity Benign epilepsy with centrotemporal spikes Generalized periodic epileptiform discharges Subacute sclerosing panencephalitis Lateralized periodic epileptiform discharges Herpes simplex encephalitis
Febrile seizures (typical/atypical) Autism with only staring episodes To differentiate - ? Seizure ? Non-epileptic event Established epilepsy – periodic EEG monitoring EEG – No role
Step 6 Switch to another monotherapy or addon Management Strategies Step 1 Step 4 Select AED Step 3 Evaluate need for Tt Step 2 Establish seizure type/syndrome Confirm Diagnosis Step 5 Start monotherapy
Management Strategies First Seizure Generalized No deficits normal EEG Wait and watch No deficits High rec risk AED trial Focal deficit Neuroimaging treat accordingly
Principles of drug therapy in epilepsy 1. Start with a single AED 2. Start with low dose and increase gradually 3. Ensure compliance 4. Increase dose gradually to maximum tolerate “As much as needed BUT as little as possible” Self evident but often forgotten 5. A seizure diary should be kept by the parents 6. AED is withdrawn after 2 year of seizure freedom.
AED of Choice Seizure First Choice Second Choice Focal seizure Oxcarbamazepine: Carbamazepine Valproate, Phenytoin Idiopathic Generalized Epilepsy • BOYS: Valproate, Phenytoin • GIRLS: Levetiracetam, Lamotrigine • Levetiracetam, Lamotrigine, Zonisamide • Valproate, Zonisamide Absence Valproate, Lamotrigine, Ethosuximide Levetiracetam, Topiramate, Zonisamide Epileptic spasms ACTH, Steroids Vigabatrine Myoclonic Valproate Levetiracetam, Topiramate, Zonisamide Tonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide Atonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide Neonatal seizures Phenobarbitone, Phenytoin Levetiracetam Benign Rolandic Epilepsy None Valproate, Cobazam
Refractory Epilepsy • Epilepsy which is uncontrolled despite adequate trials of three first line AEDs and when it disrupts developmental progress or normal childhood activity
Surgical Remedies Hemispheric epilepsies – hemispherecomy/hemispherotomy Neocortical resection, multilobar resection Mesial temporal lobe epilepsy caused often by hippocampal sclerosis Drop attacks with injuries respond well to corpus callosotomy Sterotactic ablation Multiple subpial transction
Antiepileptic Drugs - Classification • Sodium channel blockers: • Fast Channel : Carbamazepine, Oxcarbazepine, Phenytoin, Fosphenytoin, Lamotrigine, Zonisamide, • Slow Channel : Lacosamide, Eslicarbazepine • Calcium channel blockers: • Low Voltage :Ethosuximide, Valpoate, Zonisamide • High Voltage:Ethosuximide, Valpoate, Zonisamide • GABA Modulators: • GABA Receptor Agonists: Clobazam, Clonazepam, Midazolam, Phenobarbital, Primidone, Benzodiazepines, Phenobarbitone, Felbamate, Levetiracetam • GABA Reuptake inhibitors: Tiagabine • GABA Transaminase Inhibitors : Vigabatrin • Potential GABA Mechanism of Action : Gabapentin, Pregabalin, Valproate (enhance glutamic acid decarboxylase (GAD)) • Glutamate blockers : Felbamate (NMDA), Topiramate(AMPA/KA), Perampanel, Levetiracetam(AMPA), Valproate (NMDA) • Carbonic anhydrase inhibitors : Topiramate and Zonisamide • SV2A-binding agents: Levetiracetam, brivaracetam • Other Mechanism of Action: Levetiracetam, Brivaracetam, Cannabidiol, Stiripentol • Neuronal Potassium Channel Openers :Ezogabine, Retigabine
Summary of Role of AEDs • Broad spectrum AEDs • CLB, LGT, TPM, ZNS – used in generalized and focal epilepsies • CLOBAZAM: Most common and effective add-on AED in many situations • LAMOTRIGENE: • Titrate slowly, otherwise bad skin rashes including SJ syndrome • Effective add-on for IGE, Absence and Focal epilepsy • TOPIRAMATE: • Effective in focal epilepsy including in infants • Can be titrated quickly • Beware of speech, memory and cognitive side effects • ZONISAMIDE: Effective in drop attacks, refractory spasms
Dose Adjustments with Weight Gain Significant Wt Gain Sz free Occasional sz only AED ceiling dose reached Continue same dose Regular Seizures AED ceiling dose reached Yes Add on AED No Increase the dose
Management of Status Epilepticus Time / Phase Treatment 0-5 min (Stabilization Phase) Ensure adequate ventilation/O2, vitals monitoring, IV line with NS, rapid assessment, blood draw 5 - 20 min (Initial Therapy Phase) • Lorazepam 4 mg (0.1 mg/kg) or diazepam 10 mg (0.2 mg/kg) over 2 minutes via second IV line or • Rectal diazepam / Intranasal midazolam / buccal midazolam 20 - 40 min (Second Therapy Phase) • IV - Fosphenytoin or Phenytoin (20 mg/kg) or Valproic acid (40 mg/kg) or Levetiracetam (60 mg/kg) single dose • IV phenobarbital (15 mg/kg) single dose 40 - 60 min (Third Therapy Phase) • ?? Repeat of 2nd line therapy; Anaesthetic doses of Thiopental, midazolam, phenobarbital or propofol with continuous EEG monitoring
AED of Choice Seizure First Choice Second Choice Focal seizure Oxcarbamazepine: Carbamazepine Valproate, Phenytoin Idiopathic Generalized Epilepsy • BOYS: Valproate, Phenytoin • GIRLS: Levetiracetam, Lamotrigine • Levetiracetam, Lamotrigine, Zonisamide • Valproate, Zonisamide Absence Valproate, Lamotrigine, Ethosuximide Levetiracetam, Topiramate, Zonisamide Epileptic spasms ACTH, Steroids Vigabatrine Myoclonic Valproate Levetiracetam, Topiramate, Zonisamide Tonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide Atonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide Neonatal seizures Phenobarbitone, Phenytoin Levetiracetam Benign Rolandic Epilepsy None Valproate, Cobazam
Take Home Message • Approach a child with seizures systematically • Seizures and epilepsy are clinical diagnoses • Well reported good EEG supports the clinical diagnosis • Use neuroimaging judiciously; avoid CT scans • Treat the patient and NOT the EEG report • Epilepsy treatment is tailor made
Role of EEG  EEG when abnormal can suggest the nature of the seizure tendency as focal or generalized, but does not determine whether or not a spell was a seizure or whether or not to treat,.  50% of patients with partial seizures show focal spikes (or slowing), up to 75% after repeat studies or sleep deprivation.  90% of patients with generalized seizures show generalized spikes, more with sleep deprivation, hyperventilation, or photic stimulation.  A normal EEG would favor partial onset seizures in a patient with epilepsy.  1-2% of nonepileptics have spikes on their EEGs.  20% of patients with spikes on the EEG do not have epilepsy.
Role of EEG in Office practice Supports the clinical diagnosis of epilepsy 1 To classify epilepsy : Focal vs Generalized epilepsy 2 To identify epilepsy syndromes 3 3 To predict recurrence risk and to prognosticate 4 4 Unexplained GDD/worsening/autistic regression 5 • K.M.Pearce, H.R. Cock, Seizure 2006
• Dr.C.S.N.Vittal
Disorders mimicking seizures... • Jitteriness in newborn • Breath holding spells in toddlers • Shuddering attacks • Syncopal attacks • Night terror • Pseudo seizures • Migraine
Nonepileptic Paroxysms Age Group Seizure Mimics Neonates • Jitteriness • Benign Sleep Myoclonus • Hyperekplexia Infants • Breath-holding spells • Infantile self-stimulation • Shuddering episodes • Infantile Tremor Syndrome • Sandifer Syndrome Age Group Seizure Mimics Children • Tics • Hypnic Jerks • Syncope – vasovagal, Long QT, etc. • Parasomnias • Psychogenic non-epileptic episodes • Migraine associated disorders • Narcolepsy-cataplexy
Antiepileptic Drugs - Classification • Sodium channel blockers: • Fast Channel : Carbamazepine, Oxcarbazepine, Phenytoin, Fosphenytoin, Lamotrigine, Zonisamide, • Slow Channel : Lacosamide, Eslicarbazepine • Calcium channel blockers: • Low Voltage :Ethosuximide, Valpoate, Zonisamide • High Voltage :Ethosuximide, Valpoate, Zonisamide • GABA Modulators: • GABA Receptor Agonists: Clobazam, Clonazepam, Midazolam, Phenobarbital, Primidone, Benzodiazepines, Phenobarbitone, Felbamate, Levetiracetam • GABA Reuptake inhibitors: Tiagabine • GABA Transaminase Inhibitors : Vigabatrin • Potential GABA Mechanism of Action : Gabapentin, Pregabalin, Valproate (enhance glutamic acid decarboxylase (GAD))
Antiepileptic Drugs - Classification • Glutamate blockers : Felbamate (NMDA), Topiramate(AMPA/KA), Perampanel, Levetiracetam(AMPA), Valproate (NMDA) • Carbonic anhydrase inhibitors : Topiramate and Zonisamide • SV2A-binding agents: Levetiracetam, brivaracetam • Other Mechanism of Action: Levetiracetam, Brivaracetam, Cannabidiol, Stiripentol • Neuronal Potassium Channel Openers :Ezogabine, Retigabine
NICE guidelines on AEDs based on seizure types Seizure Type First-Line AEDs Adjunctive AEDs GTCS Carbamazepine Lamotrigine Oxcarbazepine Sodium valproate Topiramate Clobazam Levetiracetam Tonic or atonic Sodium valproate Lamotrigine Absene Ethosuximide Lamotrigene Sodium valproate Seizure Type First-Line AEDs Adjunctive AEDs Myoclonic Levetiracetam Sodium valproate Topiramate Focal Carbamazepine Lamotrigine Levetiracetam Oxcarbazepine Sodium valproate Clobazam Gabapentine Topiramate
Phenytoin • Causes voltage-dependent block of voltage gated sodium channels possibly by promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. • The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. • Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of generalized tonic-clonic seizures
Phenytoin • Anticonvulsant effect: 10–20 µg/mL; • Medical uses • Prophylactic management of tonic- clonic seizures with complex symptomatology (psychomotor seizures • Effective in controlling partial seizures with autonomic symptoms. • Status epilepsy • Digoxin toxicity, atrial tachycardia • Trigeminal neuralgia • Not recommended • Pregnancy : craniofacial deformities, lethal fetal hydantoin syndrome • Side Effects • swelling and bleeding of the gums • Hypertrichosis, SJ syndrome • Hypotension • Nystagmus, diplopia • Cerebellar atrophy • Peripheral neuritis • Contraindications • Liver disease • Not recommend breast feeding because low concentrations of phenytoin are excreted in breast milk. • Sinus bradycardia, AV blocks – IV adm not recommended • Pregnancy : craniofacial deformities, lethal fetal hydantoin syndrome
Newer AEDs • Felbamate 1993 • Gabapentin 1993 • Lamotrigine 1994 • Topiramate 1996 • Tiagabine 1998 • Levetiracetam 1999 • Oxcarbazepine 2000 • Zonisamide 2000 • Pregabalin 2005 • Lacosamide 2008 • Eslicarbazepine 2009 • Retigabine 2011
Dose Adjustments with Weight Gain Significant Wt Gain Sz free Occasional sz only AED ceiling dose reached Continue same dose Regular Seizures AED ceiling dose reached Yes Add on AED No Increase the dose
a amino hydroxy methyl isoxazole propionic acid
AEDs & action
FELBAMATE • Mechanism of action – • Sodium channel blockade, • potentiation of GABA a mediated inhibition and antagonism of NMDA mediated responses. • Indications – • Not indicated as a First line agent. • Add-on treatment of Lennox-Gestaut Syndrome and partial and secondary generalised seizure refractory to other agents. • Dosage: • 15mg/kg (children) • Significant drug interactions: • increases Phenytoin, valproate levels • lowers carbamazepine and steroid levels • valproate decreases rate of Felbamate elimination • Highly effective in severe refractory cases, but use limited by hepatic and haematological toxicity.
GABAPENTIN • Mechanism of action – • Modulates neurotransmitter release by binding to α2-δ subunit of voltage gated Ca channels. This closes N and P/Q pre-synaptic calcium channels, diminishing excessive neuronal activity and neurotransmitter release • Indications – • Adjunctive therapy or monotherapy of partial or secondary generalized seizures. • also used in Neuropathic Pain, postherpetic neuralgia and diabetic neuropathy. • Dosage: • Significant drug interactions: • Antacid can reduce absorption by abt 20%. • Adverse effects – • Drowsiness (24.4%), dizziness (20.3%), ataxia (17%), headache (15%), tremor, diplopia, nausea, vomiting, non-pitting pedal edema, weight gain • Effective in focal epilepsy but may aggravate generalized epilepsy. • Spectrum of efficacy restricted to partial epilepsies
LAMOTRIGINE • Mechanism of action – • Blockade of voltage dependent sodium and calcium channels. • Indications – • Adjunctive therapy and monotherapy of partial seizures (with or without secondary generalization), other generalized epilepsy syndromes, including Lennox-Gastaut Syndrome • Dosage: • Significant drug interactions: • Serum Lamotrigine levels are increased by Valproic acid as Valproate reduces rate of Lamotrigine elimination • adverse effects – • Dizziness, diplopia, ataxia, blurred vision, somnolence, insomnia, headache, nausea, asthenia, skin rash • Useful drug which can be used as 1st or 2nd line monotherapy, or as adjunctive therapy in treatment of partial seizures and occasionally in generalised epilepsy syndromes. • Main disadvantage is need for slow-dose escalation.
TOPIRAMATE • Mechanism of action – • Blockade of voltage dependent na and ca channels • Potentiation of GABA mediated inhibition at GABA A receptors, • Reduction of excitatory action of glutamate via AMPA receptors, - • Inhibition of carbonic anhydrase. • Indications – • Adjunctive therapy or monotherapy of partial and secondary GTCS. Also useful for Lennox- Gastaut Syndrome and primary • Dosage: • Significant drug interactions: • Serum Topiramate levels are reduced by enzyme inducing AEDs (Phenytoin, carbamazepine, phenobarbital). • Topiramate may increase serum Phenytoin levels. • Adverse effects – • Dizziness, ataxia, somnolence, paraesthesia, tremor, somnolence, cognitive dysfunction, confusion, agitation, amnesia, depression, headache, nausea, diarrhoea, diplopia, weight loss. A very useful drug with relatively broad spectrum efficacy. - Safe in pregnancy. - Main advantage is high responder rates. - Main disadvantage is CNS adverse effects. - Dose reduction required in renal diseases.
LEVETIRACETAM • Mechanism of action – • Binds to Synaptic Vesicle 2A (SV2A) protein. Precise mechanism by which this binding acts is unknown but is likely to involve inhibition of neurotransmitter release from nerve end terminals. • Indications – • First- line and adjunctive therapy of partial-onset seizures. • Adjunctive and, possibly, first line therapy of GTCS and Myoclonic seizures associated with idiopathic generalized epilepsies. • Dosage: • 20-60 mg/kg/day. Tt may be started with 10-20 mg/kg/day and adjusted according to response , by increments of 10-20 mg/kg/day every 2 weeks • Significant drug interactions: • Serum Levetiracetam levels are reduced by enzyme inducing AEDs (Phenytoin, carbamazepine, phenobarbital) by about 20-30 %. • Adverse effects – • Dizziness, ataxia, somnolence (10%), asthenia, infection, nervousness, irritability, behavioural and Psychiatric disorders (12.9% vs 6.2% of placebo patients), suicidal behaviour • Main advantage is Relatively broad spectrum activity, good tolerability, and lack of clinically significant drug interactions. • Main disadvantage is efficacy in some generalized seizure types and epilepsy syndrome unproven. Behavioural and psychiatric adverse effects
OXCARBAZEPINE • Mechanism of action – • Blockade of voltage gated Na channels and N and P type calcium channels. • Indications – • Adjunctive therapy or monotherapy for partial and secondary generalized seizures. • Also useful to treat primary generalized tonic clonic . • Dosage: • 20-60 mg/kg/day. Tt may be started with 10-20mg/kg/day and adjusted according to response , by increments of 10-20 mg/kg/day every 2 weeks • Significant drug interactions: • Serum Oxcarbazepine levels are reduced by enzyme inducing AEDs by promoting its clearance. • Oxcarbazepine may increase the levels of phenytoin and Phenobarbital. • Main advantage is that it is better tolerated and has fewer interactions than carbamazepine. Risk of hepatotoxicity is estimated to be lower than carbamazepine. • Main disadvantage is efficacy spectrum restricted to partial epilepsies. Higher incidence of hyponatremia compared with carbamazepine. • Not indicated for absence, myoclonic and other types of generalized seizures other than tonic-clonic seizures and indeed may exacerbate them.
ZONISAMIDE • Mechanism of action – • Multiple including blockade of voltage • gated Na channels, blockade of T-type calcium channels, potentiation of GABAergic transmission and • inhibition of Carbonic anhydrase. • Indications – • Adjunctive therapy for partial and secondary generalized seizures. • May also be used as adjunctive therapy in primary eneralized seizures. Myoclonic Epilepsies • Dosage: • Significant drug interactions: • Serum Zonisamide levels are reduced by enzyme inducing AEDs. • Administration with food does not reduce the extent but decreases the rate of absorption. • increase in the incidence of renal stones if given with topiramate (CA Inhibitors) • adverse effects – • Agitation, irritability, confusion, depression, anorexia, Weight loss, Nephrolithiasis, skin rashes (including Stevens Jonhnson Syndrome), blood dyscrasias and hypersensitivity reaction. • broad spectrum of Efficacy Main advantage Main disadvantage is CNS adverse effects. • No proven safety in Pregnancy,
ESLICARBAZEPINE ACETATE • Mechanism of action – • Blockade of voltage gated sodium channels resulting in stabilization of hyper- excitable neuronal membranes. • Indications – • Adjunctive therapy for partial seizures. • Dosage: • Significant drug interactions: • Enzyme inducing AEDs reduce serum Eslicarbazepine levels. Eslicarbazepine acetate decreases the levels of OCPs. • Adverse effects – • Dizziness , blurred vision, headache, nausea, diplopia, nausea, vomiting, visual disturbances • Main advantage is usually well tolerated, once daily dosing • Main disadvantage is limited clinical experience, efficacy spectrum probably restricted to partial epilepsies.
RETIGABINE • Mechanism of action – • Activation of voltage gated neuronal Potassium channels [KCNQ (kv7)], resulting in enhanced M-current, and thereby stabilization of resting membrane potential. • Indications – • Adjunctive therapy for refractory partial-onset seizure. • Dosage: • Significant drug interactions: • Retigabine increases Lamotrigine levels by about 20%. • Enzyme inducing AEDs reduce serum Lacosamide levels by approx 30 %. • Adverse effects – • Dizziness , somnolence, fatigue, confusion, dysarthria, confusion, tremor, urinary hesitancy/retention. • Main advantage is clearly defined dose related efficacy, low interaction potential. • Main disadvantage is need for gradual titration and for frequent dosing, CNS adverse effects
Perampanel • A highly selective, non competitive AMPA (a-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid) receptor antagonist. • The mechanism of action • Reduces neuronal hyperexcitability by targeting glutamate activity at postsynaptic AMPA receptors. • Approved as an adjunct therapy for focal-onset seizures and primary generalized tonic-clonic seizures (GTCS) in patients aged 12 years and older • Once-daily dosing and has a half-life of 106 hours. • Common adverse events are dizziness, fatigue, headache and somnolence. Specific adverse effects to monitor are neuropsychiatric events, including aggression, anger, homicidal ideation, hostility, and irritability
Cannabidiol (CBD) • Reduces neuronal hyperexcitability through a unique multimodal mechanism of action. • It antagonizes G protein-coupled receptor 55 (GPR55) at excitatory synapses. • The inhibition of intracellular calcium release decreases excitatory currents and seizure activity. • CBD desensitizes transient receptor potential vanilloid type 1 (TRPV1) channels The resultant decrease in extracellular calcium influx decreases neurotransmission. • CBD inhibits equilibrative nucleoside transporters (ENT1), reducing adenosine reuptake. The increase in extracellular adenosine reduces hyper excitability and neurotransmission. • NICE guidelines published in December 2019 states that cannabidiol with clobazam is recommended as an option for treating seizures associated with Dravet syndrome and LGS in patients aged 2 years and older,
Ketogenic Diet and Atkin’s diet • The ketogenic diet (KD) is a stringently controlled high fat and low protein/carbohydrate diet given with/without a restricted fluid intake to maintain ketosis on a long term basis. • It has been shown that it is more efficacious than newer AEDs in controlling refractory seizures • A ‘ketogenic’ ratio of at least 3:1 is usually needed for maintenance of a good state of ketosis and optimal seizure control
Surgical Remedies Hemispheric epilepsies Developmental tumors, cortical dysplasias, AVMs Mesial temporal lobe epilepsy caused often by hippocampal sclerosis Drop attacks with injuries respond well to corpus callosotomy
Take Home Message • Approach a child with seizures systematically • Seizures and epilepsy are clinical diagnoses • Well reported good EEG supports the clinical diagnosis • Use neuroimaging judiciously; avoid CT scans • Treat the patient and NOT the EEG report • Epilepsy treatment is tailor made
• Dr.C.S.N.Vittal

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Epilepsy in Children.pptx

  • 1.
  • 2.
    Seizure (Latin sacire, “totake possession of”) A transient occurrence of signs and/or symptoms resulting from abnormal excessive or synchronous neuronal activity in the brain.
  • 3.
    Epilepsy Epilepsy is adisorder characterized by two or more unprovoked seizures occurring more than 24 hours apart beyond neonatal period.
  • 4.
    • A seizureis the event Seizure vs Epilepsy • Epilepsy is the disease associated with spontaneously recurring seizures
  • 5.
    Convulsion A convulsion isany seizure (not necessarily epileptic) characterized by excessive, abnormal muscle contractions, which are usually bilateral.
  • 6.
    Epilepsy – newdefinition Epilepsy is a disease of the brain defined by any of the following: 1. A least two unprovoked (or reflex) seizures occurring >24 h apart 2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years 3. Diagnosis of an epilepsy syndrome • Robert S fisher et al; A practical clinical definition of epilepsy: Epilepsia, 55($):475-482, 2014
  • 7.
    Risk of epilepsyafter 2 seizures • Hauser et al. Risk of recurrent seizures after two unprovoked seizures. NEJM 1998;338:429.
  • 8.
    Seizures Focal The first clinicaland electroencephalographic (EEG) changes suggest initial activation of a system of neurons limited to part of one cerebral hemisphere The first clinical and EEG changes indicate synchronous involvement of all of both hemispheres Generalized
  • 9.
    Some terminology • DrNeeta Naik, Guidelines for Diagnosis and Management of Childhood Epilepsy; Expert Committee On Pediatric Epilepsy, IAP; Ind Ped, Vol 46 Aug 17, 2009: 681-698
  • 11.
  • 12.
  • 13.
    Status Epilepsy (>100/ 100000 population) • Recurrent epileptic seizures continuing for more than 30 minutes without full recovery of consciousness before the next seizure begins, or continu- ous clinical and/or electrical seizure activity lasting for more than 30 minutes whether or not consciousness is impaired’ Clinical Definition New Operational Definition (children > 5 yrs) • “Greater than or equal to 5 minutes of continuous seizures or two or more discrete seizures between which there is incomplete recovery of consciousness.” • A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Eugen Trinka, et al; Epilepsia, 56(10):1515–1523, 2015 doi: 10.1111/epi.13121
  • 14.
    Time definition forCSE for treatment purposes (Operational definition) Key time periods in natural history of seizure 0 5 15 30 Interval within which most seizures spontaneously stop Optimum interval for initiation of rescue therapy Time definition for CSE for epidemiological, pathophysiological and outcome purposes
  • 15.
    Status Epilepsy -ILAE A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Eugen Trinka, et al; Epilepsia, 56(10):1515–1523, 2015 doi: 10.1111/epi.13121 Tonic-Clonic Focal with impaired consciousness Absences Point 1 (t1) the earliest time when treatment should be started. 5 min 10-15 min 15 min Point 2 (t2) when long-term consequences, such as neuronal injury, neuronal death 30 min > 60 min Unknown
  • 16.
    Convulsive Status epilepticus Complexpartial, absence, myoclonic status, epilepsia partialis continua, and neonatal status epilepticus, confusional state, hyperactivity with behavioral problems, fluctuating impairment of consciousness with at times unsteady sitting or walking, fluctuating mental status, confusional state, hallucinations, paranoia, aggressiveness catatonia, and or psychotic symptoms. Non-convulsive Status epilepticus Status Epilepticus Generalized tonic, clonic, or tonic–clonic
  • 17.
    Mechanisms which UnderlieSeizure Generation • Abnormalities at the cell membrane level (ion channels and receptors) and in neuronal circuits • 3 main classes of voltage gated ion channels have been described: Na+, Ca2+, K+. • Sodium currents are involved in the generation of action potentials. • Potassium currents cause hyperpolarization and hence stabilize the neuronal membrane. • Both calcium and sodium currents are involved in the generation of burst discharges, generated by certain classes of neurones when excited. • Gamma amino butyric acid (GABA) and glycine are inhibitory neurotransmitters while glutamate and aspartate are excitatory neurotransmitters. • A useful, though simplistic model of epilepsy is that it involves an imbalance of excitatory and inhibitory neurotransmitter systems within the CNS.
  • 18.
    Mechanisms which UnderlieSeizure Generation 2. Involves an imbalance of excitatory (glutamate and aspartate) and inhibitory (Gamma amino butyric acid and glycine ) neurotransmitter systems within the CNS. 1. Abnormalities at the cell membrane level (ion channels and receptors) and in neuronal circuits
  • 19.
    The 2017 ILAEClassification of Seizures Robert S. Fisher, MD, PhD Maslah Saul MD Professor of Neurology Director, Stanford Epilepsy Center In 2017, the ILAE released a new classification of seizure types, largely based upon the existing classification formulated in 1981.
  • 20.
    Motor Tonic-clonic Other motor Non-Motor (Absence) UnknownOnset Motor Non-Motor focal to bilateral tonic-clonic Generalized Onset Focal Onset Motor Tonic-clonic Other motor Non-Motor ILAE 2017 Classification of Seizure Types Basic Version 1 Unclassified 2 Aware Impaired Awareness From Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia doi: 10.1111/epi.13671 1 Definitions, other seizure types and descriptors are listed in the accompanying paper & glossary of terms 2 Due to inadequate information or inability to place in other categories
  • 21.
    Motor tonic-clonic clonic tonic myoclonic myoclonic-tonic-clonic myoclonic-atonic atonic epileptic spasms2 Non-Motor (absence) typical atypical myoclonic eyelidmyoclonia Unknown Onset Motor Onset automatisms atonic2 clonic epileptic spasms2 hyperkinetic myoclonic tonic Non-Motor Onset autonomic behavior arrest cognitive emotional sensory focal to bilateral tonic-clonic Generalized Onset Focal Onset Aware Impaired Awareness Motor tonic-clonic epileptic spasms Non-Motor behavior arrest ILAE 2017 Classification of Seizure Types Expanded Version Unclassified3 2 These could be focal or generalized, with or without alteration of awareness 3 Due to inadequate information or inability to place in other categories From Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia doi: 10.1111/epi.13671
  • 22.
    focal onset aware impairedawareness motor onset (seizures with physical movement) automatisms atonic clonic epileptic spasms hyperkinetic myoclonic tonic non-motor onset (seizures without physical movement) autonomic behaviour arrest congnitive emotional sensory motor onset (seizures with physical movement) automatisms atonic clonic epileptic spasms hyperkinetic myoclonic tonic non-motor onset (seizures without physical movement) autonomic behaviour arrest congnitive emotional sensory focal to bilateral tonic clonic seizure (sec generalized seizures) seizures start in, and affect one part of the brain focal aware seizures (simple partial seizures) focal impaired awareness seizures (complex partial seizures)
  • 23.
    generalized onset seizures startin, and affect both sides of the brain at once and happen without warning motor (with physical movement) non-motor (absence) (without any physical movement) Motor tonic-clonic clonic tonic myoclonic myoclonic-tonic-clonic myoclonic-atonic atonic epileptic spasms2 Non-Motor (absence) typical (3 Hz spike & slow wave ) atypical (1-2 Hz spike & slow wave with head atonia and myoclonus) myoclonic eyelid myoclonia
  • 24.
    unknown onset (cryptogenic epilepsy)unclassified motor (with physical movement) non-motor (without any physical movement) if doctors are not sure where in the brain the seizure starts If there is not enough information available about the person’s seizure or because of the nature of the seizure.
  • 25.
    Etiology of Seizures– Neonatal Period • Birth asphyxia or trauma • Intracranial hemorrhage • Hypoglycemia • Hypocalcaemia or hypomagnesemia • Infections: meningitis, septicemia, tetanus neonatorum • Inborne errors of metabolism • Pyridoxin dependent seizures • Maternal withdrawal of medications • Accidental injection of local
  • 26.
    Text Text Etiology of Seizures– Beyond Neonatal Period • Vascular: hemorrhage , AV malformations, intracranial thrombosis • Cerebral malformation: neurocutaneous syndromes, neuronal migration disorders • Drugs/Poisons: Phenothiazines, lead salicylates, phenytoin, CO, strychnine • Miscellaneous: Hypertensive encephalopathy, gray matter degeneration, storage disorders • Simple febrile convulsions • Epilepsy syndromes • Infections: meningitis, encephalitis, Reye syndrome, cerebral malaria • Metabolic causes: Dyselectrolytemia, hypocalcemiam hypomagnesemia, IEM • Space occupying lesions: Neoplasm, brain abscess, tuberculoma, cysticercosis • Trauma:
  • 27.
    Febrile Seizures FS isa seizure occurring in childhood after one month of age, associated with a febrile illness that is not caused by an infection of the central nervous system ILAE Definition: Febrile seizures are seizures that occur between the ages of 6 and 60 mo (peak 12-18 mo) with a temperature of 38°C (100.4°F) or higher, that are not the result of CNS infection or any metabolic imbalance, and that occur in the absence of a history of prior afebrile seizures Nelson Text Book Definition:
  • 28.
    Febrile Seizures –Types Simple • Primary generalized, • usually tonic–clonic, • attack associated with fever • Lasting for a maximum of 15 min • Do not recurrent within a 24- hr period • Do not have an increased risk of mortality Complex • Focal • Prolonged (>15 min) • Recurs within 24 hours • 2-fold long-term increase in mortality rates, as compared with the general population, over the subsequent 2 yr, probably sec to a coexisting pathology
  • 29.
    Febrile status epilepticus …is defined as one lasting over 30 minutes. Febrile seizure plus When the febrile seizures continue after age 5 or other types of seizure develop. FS+ usually end in early adolescence. ... • Febrile infection–related epilepsy (FIRES): In children >5 yr) usually male children and associated with an encephalitis-like illness but without an identifiable infectious agent. Children with FIRES were previously normal but subsequently develop difficult-to-treat epilepsy. • Generalised epilepsy with febrile seizures plus (GEFS+): Children may go on to have febrile seizures well beyond 6 yrs age, even into adult life. They may also develop other seizure types not associated with a high temperature. An epileptic syndrome.
  • 30.
    Risk factors forRecurrence No risk factors 12% 1 risk factor 25-50% 2 risk factors 50-59% 3 or more risk factors 73-100% Febrile Seizures – Risk Factors MAJOR • Age < 1 yr • Duration of fever < 24 hr • Fever > 38-390C (100.4 – 102.20F) MINOR • Family history of febrile seizure • Family history of epilepsy • Complex febrile seizure • Daycare • Male gender • Lower serum sodium at time of presentation • Nelson Textbook of Pediatrics, 21E
  • 31.
    Epilepsy Syndromes Male,2-13 yrs Mostly nocturnal Motor & somatosensory – older children Hemiclonic / GTCS – younger children Most AEDs effective, Recovery before 15-16 yrs Commonest generalized epilepsy in 5-16 yrs olds GTCSs 3-6 Hz generalized polyspikes and waves in EEG Improve after 4th decade 3-10 %, Genetic pre disposistion Male preponderance, Onset 1-8 yrs Poor prognosis Hypsarrhythmia , Tuberous sclerosis Typically in 3-5 yrs age group Severe, Complex epilepsy Multiple concurrent seizure types Cognitive dysfunction Benign Rolandic Epilepsy Juvenile Myoclonic Epilepsy West Syndrome (Infantile Spasms) Lenox Gestaut Syndrome
  • 32.
    Benign epilepsy withoccipital spikes • headaches that occur independently or postictally (epilepsy–migraine sequence) Panayiotopoulos type •Occur in early childhood •Manifests with focal seizures •Impaired awareness •Ictal vomiting Gastaut type •appear in later childhood •focal seizures with •impaired awareness •Visual auras, and •migraine
  • 33.
    Seizure Evaluation on First Visit 1 Seizure/ seizure mimic ? 2 Is it unprovoked / provoked seizure? 3 Generalized / focal seizure? 4 Etiology? 5 Any associated comorbidities? 6 Treatment received till now?
  • 34.
    Role of Imaging •MRI is the imaging modality of choice! But not urgent • Significant cognitive or motor impairment of unknown etiology • Unexplained abnormalities on neurologic examination • Focal seizure with or without secondary generalization • EEG that does not represent a benign partial epilepsy or primary generalized epilepsy • Seizure in children under 1 year of age • If MRI can not be done, better don’t do imaging!! - Epilepsia, 50(9): 2147-2153, 2009
  • 35.
    Quietly sitting, relaxed, eyesclosed 20-60 mV Most common waves. During mental thought & activity 2-20 mV 20-100 mV Common in children. Displeasure, pleasure, and drowsiness Very irregular &slow waves. Deep sleep in most people 20-200 mV Gamma ( g ) 36-44 Hz 3-5 mV With sudden sensory stimuli
  • 36.
    Role of EEG •EEG when abnormal can suggest the nature of the seizure tendency as focal or generalized, but does not determine whether or not a spell was a seizure or whether or not to treat,. • 50% of patients with partial seizures show focal spikes (or slowing), up to 75% after repeat studies or sleep deprivation. • 90% of patients with generalized seizures show generalized spikes, more with sleep deprivation, hyperventilation, or photic stimulation. • A normal EEG would favor partial onset seizures in a patient with epilepsy. • 1-2% of nonepileptics have spikes on their EEGs. • 20% of patients with spikes on the EEG do not have epilepsy.
  • 37.
    Role of EEGin Office practice Supports the clinical diagnosis of epilepsy 1 To classify epilepsy : Focal vs Generalized epilepsy 2 To identify epilepsy syndromes 3 3 To predict recurrence risk and to prognosticate 4 4 Unexplained GDD/worsening/autistic regression 5 • K.M.Pearce, H.R. Cock, Seizure 2006
  • 38.
    A. Onset ofa tonic seizure showing generalized repetitive sharp activity with synchronous onset over both hemispheres. B. Burst of repetitive spikes occurring with sudden onset in the right temporal region during a clinical spell characterized by transient impairment of external awareness. C. Generalized 3-Hz spike-wave activity occurring synchronously over both hemispheres during an absence (petit mal) attack. Horizontal calibration: • MJ Aminoff [ed]: Aminoff’s Electrodiagnosis in Clinical Neurology, 6th ed. Oxford, Elsevier Saunders, 2012.)
  • 39.
    EEG interpretation –in general Finding Likely Diagnosis Spike followed by slow waves Interictal pattern of epilepsy 3 Hz spike and wave discharges; provoked by hyperventilation Absence epilepsy Chaotic high voltage of poyspikes with photosensitivity West syndrome Spike wave complexes in Rolandic areas Juvenile myoclonic epilepsy Brief bursts of polyspikes with photosensitity Benign epilepsy with centrotemporal spikes Generalized periodic epileptiform discharges Subacute sclerosing panencephalitis Lateralized periodic epileptiform discharges Herpes simplex encephalitis
  • 40.
    Febrile seizures (typical/atypical) Autismwith only staring episodes To differentiate - ? Seizure ? Non-epileptic event Established epilepsy – periodic EEG monitoring EEG – No role
  • 41.
    Step 6 Switch toanother monotherapy or addon Management Strategies Step 1 Step 4 Select AED Step 3 Evaluate need for Tt Step 2 Establish seizure type/syndrome Confirm Diagnosis Step 5 Start monotherapy
  • 42.
    Management Strategies First Seizure Generalized Nodeficits normal EEG Wait and watch No deficits High rec risk AED trial Focal deficit Neuroimaging treat accordingly
  • 43.
    Principles of drugtherapy in epilepsy 1. Start with a single AED 2. Start with low dose and increase gradually 3. Ensure compliance 4. Increase dose gradually to maximum tolerate “As much as needed BUT as little as possible” Self evident but often forgotten 5. A seizure diary should be kept by the parents 6. AED is withdrawn after 2 year of seizure freedom.
  • 44.
    AED of Choice SeizureFirst Choice Second Choice Focal seizure Oxcarbamazepine: Carbamazepine Valproate, Phenytoin Idiopathic Generalized Epilepsy • BOYS: Valproate, Phenytoin • GIRLS: Levetiracetam, Lamotrigine • Levetiracetam, Lamotrigine, Zonisamide • Valproate, Zonisamide Absence Valproate, Lamotrigine, Ethosuximide Levetiracetam, Topiramate, Zonisamide Epileptic spasms ACTH, Steroids Vigabatrine Myoclonic Valproate Levetiracetam, Topiramate, Zonisamide Tonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide Atonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide Neonatal seizures Phenobarbitone, Phenytoin Levetiracetam Benign Rolandic Epilepsy None Valproate, Cobazam
  • 45.
    Refractory Epilepsy • Epilepsywhich is uncontrolled despite adequate trials of three first line AEDs and when it disrupts developmental progress or normal childhood activity
  • 46.
    Surgical Remedies Hemispheric epilepsies– hemispherecomy/hemispherotomy Neocortical resection, multilobar resection Mesial temporal lobe epilepsy caused often by hippocampal sclerosis Drop attacks with injuries respond well to corpus callosotomy Sterotactic ablation Multiple subpial transction
  • 47.
    Antiepileptic Drugs -Classification • Sodium channel blockers: • Fast Channel : Carbamazepine, Oxcarbazepine, Phenytoin, Fosphenytoin, Lamotrigine, Zonisamide, • Slow Channel : Lacosamide, Eslicarbazepine • Calcium channel blockers: • Low Voltage :Ethosuximide, Valpoate, Zonisamide • High Voltage:Ethosuximide, Valpoate, Zonisamide • GABA Modulators: • GABA Receptor Agonists: Clobazam, Clonazepam, Midazolam, Phenobarbital, Primidone, Benzodiazepines, Phenobarbitone, Felbamate, Levetiracetam • GABA Reuptake inhibitors: Tiagabine • GABA Transaminase Inhibitors : Vigabatrin • Potential GABA Mechanism of Action : Gabapentin, Pregabalin, Valproate (enhance glutamic acid decarboxylase (GAD)) • Glutamate blockers : Felbamate (NMDA), Topiramate(AMPA/KA), Perampanel, Levetiracetam(AMPA), Valproate (NMDA) • Carbonic anhydrase inhibitors : Topiramate and Zonisamide • SV2A-binding agents: Levetiracetam, brivaracetam • Other Mechanism of Action: Levetiracetam, Brivaracetam, Cannabidiol, Stiripentol • Neuronal Potassium Channel Openers :Ezogabine, Retigabine
  • 49.
    Summary of Roleof AEDs • Broad spectrum AEDs • CLB, LGT, TPM, ZNS – used in generalized and focal epilepsies • CLOBAZAM: Most common and effective add-on AED in many situations • LAMOTRIGENE: • Titrate slowly, otherwise bad skin rashes including SJ syndrome • Effective add-on for IGE, Absence and Focal epilepsy • TOPIRAMATE: • Effective in focal epilepsy including in infants • Can be titrated quickly • Beware of speech, memory and cognitive side effects • ZONISAMIDE: Effective in drop attacks, refractory spasms
  • 50.
    Dose Adjustments withWeight Gain Significant Wt Gain Sz free Occasional sz only AED ceiling dose reached Continue same dose Regular Seizures AED ceiling dose reached Yes Add on AED No Increase the dose
  • 53.
    Management of StatusEpilepticus Time / Phase Treatment 0-5 min (Stabilization Phase) Ensure adequate ventilation/O2, vitals monitoring, IV line with NS, rapid assessment, blood draw 5 - 20 min (Initial Therapy Phase) • Lorazepam 4 mg (0.1 mg/kg) or diazepam 10 mg (0.2 mg/kg) over 2 minutes via second IV line or • Rectal diazepam / Intranasal midazolam / buccal midazolam 20 - 40 min (Second Therapy Phase) • IV - Fosphenytoin or Phenytoin (20 mg/kg) or Valproic acid (40 mg/kg) or Levetiracetam (60 mg/kg) single dose • IV phenobarbital (15 mg/kg) single dose 40 - 60 min (Third Therapy Phase) • ?? Repeat of 2nd line therapy; Anaesthetic doses of Thiopental, midazolam, phenobarbital or propofol with continuous EEG monitoring
  • 54.
    AED of Choice SeizureFirst Choice Second Choice Focal seizure Oxcarbamazepine: Carbamazepine Valproate, Phenytoin Idiopathic Generalized Epilepsy • BOYS: Valproate, Phenytoin • GIRLS: Levetiracetam, Lamotrigine • Levetiracetam, Lamotrigine, Zonisamide • Valproate, Zonisamide Absence Valproate, Lamotrigine, Ethosuximide Levetiracetam, Topiramate, Zonisamide Epileptic spasms ACTH, Steroids Vigabatrine Myoclonic Valproate Levetiracetam, Topiramate, Zonisamide Tonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide Atonic Valproate, Lamotrigine Levetiracetam, Topiramate, Zonisamide Neonatal seizures Phenobarbitone, Phenytoin Levetiracetam Benign Rolandic Epilepsy None Valproate, Cobazam
  • 55.
    Take Home Message •Approach a child with seizures systematically • Seizures and epilepsy are clinical diagnoses • Well reported good EEG supports the clinical diagnosis • Use neuroimaging judiciously; avoid CT scans • Treat the patient and NOT the EEG report • Epilepsy treatment is tailor made
  • 56.
    Role of EEG EEG when abnormal can suggest the nature of the seizure tendency as focal or generalized, but does not determine whether or not a spell was a seizure or whether or not to treat,.  50% of patients with partial seizures show focal spikes (or slowing), up to 75% after repeat studies or sleep deprivation.  90% of patients with generalized seizures show generalized spikes, more with sleep deprivation, hyperventilation, or photic stimulation.  A normal EEG would favor partial onset seizures in a patient with epilepsy.  1-2% of nonepileptics have spikes on their EEGs.  20% of patients with spikes on the EEG do not have epilepsy.
  • 57.
    Role of EEGin Office practice Supports the clinical diagnosis of epilepsy 1 To classify epilepsy : Focal vs Generalized epilepsy 2 To identify epilepsy syndromes 3 3 To predict recurrence risk and to prognosticate 4 4 Unexplained GDD/worsening/autistic regression 5 • K.M.Pearce, H.R. Cock, Seizure 2006
  • 58.
  • 59.
    Disorders mimicking seizures... •Jitteriness in newborn • Breath holding spells in toddlers • Shuddering attacks • Syncopal attacks • Night terror • Pseudo seizures • Migraine
  • 60.
    Nonepileptic Paroxysms Age GroupSeizure Mimics Neonates • Jitteriness • Benign Sleep Myoclonus • Hyperekplexia Infants • Breath-holding spells • Infantile self-stimulation • Shuddering episodes • Infantile Tremor Syndrome • Sandifer Syndrome Age Group Seizure Mimics Children • Tics • Hypnic Jerks • Syncope – vasovagal, Long QT, etc. • Parasomnias • Psychogenic non-epileptic episodes • Migraine associated disorders • Narcolepsy-cataplexy
  • 61.
    Antiepileptic Drugs -Classification • Sodium channel blockers: • Fast Channel : Carbamazepine, Oxcarbazepine, Phenytoin, Fosphenytoin, Lamotrigine, Zonisamide, • Slow Channel : Lacosamide, Eslicarbazepine • Calcium channel blockers: • Low Voltage :Ethosuximide, Valpoate, Zonisamide • High Voltage :Ethosuximide, Valpoate, Zonisamide • GABA Modulators: • GABA Receptor Agonists: Clobazam, Clonazepam, Midazolam, Phenobarbital, Primidone, Benzodiazepines, Phenobarbitone, Felbamate, Levetiracetam • GABA Reuptake inhibitors: Tiagabine • GABA Transaminase Inhibitors : Vigabatrin • Potential GABA Mechanism of Action : Gabapentin, Pregabalin, Valproate (enhance glutamic acid decarboxylase (GAD))
  • 62.
    Antiepileptic Drugs -Classification • Glutamate blockers : Felbamate (NMDA), Topiramate(AMPA/KA), Perampanel, Levetiracetam(AMPA), Valproate (NMDA) • Carbonic anhydrase inhibitors : Topiramate and Zonisamide • SV2A-binding agents: Levetiracetam, brivaracetam • Other Mechanism of Action: Levetiracetam, Brivaracetam, Cannabidiol, Stiripentol • Neuronal Potassium Channel Openers :Ezogabine, Retigabine
  • 63.
    NICE guidelines onAEDs based on seizure types Seizure Type First-Line AEDs Adjunctive AEDs GTCS Carbamazepine Lamotrigine Oxcarbazepine Sodium valproate Topiramate Clobazam Levetiracetam Tonic or atonic Sodium valproate Lamotrigine Absene Ethosuximide Lamotrigene Sodium valproate Seizure Type First-Line AEDs Adjunctive AEDs Myoclonic Levetiracetam Sodium valproate Topiramate Focal Carbamazepine Lamotrigine Levetiracetam Oxcarbazepine Sodium valproate Clobazam Gabapentine Topiramate
  • 64.
    Phenytoin • Causes voltage-dependentblock of voltage gated sodium channels possibly by promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. • The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. • Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of generalized tonic-clonic seizures
  • 65.
    Phenytoin • Anticonvulsant effect:10–20 µg/mL; • Medical uses • Prophylactic management of tonic- clonic seizures with complex symptomatology (psychomotor seizures • Effective in controlling partial seizures with autonomic symptoms. • Status epilepsy • Digoxin toxicity, atrial tachycardia • Trigeminal neuralgia • Not recommended • Pregnancy : craniofacial deformities, lethal fetal hydantoin syndrome • Side Effects • swelling and bleeding of the gums • Hypertrichosis, SJ syndrome • Hypotension • Nystagmus, diplopia • Cerebellar atrophy • Peripheral neuritis • Contraindications • Liver disease • Not recommend breast feeding because low concentrations of phenytoin are excreted in breast milk. • Sinus bradycardia, AV blocks – IV adm not recommended • Pregnancy : craniofacial deformities, lethal fetal hydantoin syndrome
  • 66.
    Newer AEDs • Felbamate1993 • Gabapentin 1993 • Lamotrigine 1994 • Topiramate 1996 • Tiagabine 1998 • Levetiracetam 1999 • Oxcarbazepine 2000 • Zonisamide 2000 • Pregabalin 2005 • Lacosamide 2008 • Eslicarbazepine 2009 • Retigabine 2011
  • 67.
    Dose Adjustments withWeight Gain Significant Wt Gain Sz free Occasional sz only AED ceiling dose reached Continue same dose Regular Seizures AED ceiling dose reached Yes Add on AED No Increase the dose
  • 68.
    a amino hydroxymethyl isoxazole propionic acid
  • 69.
  • 70.
    FELBAMATE • Mechanism ofaction – • Sodium channel blockade, • potentiation of GABA a mediated inhibition and antagonism of NMDA mediated responses. • Indications – • Not indicated as a First line agent. • Add-on treatment of Lennox-Gestaut Syndrome and partial and secondary generalised seizure refractory to other agents. • Dosage: • 15mg/kg (children) • Significant drug interactions: • increases Phenytoin, valproate levels • lowers carbamazepine and steroid levels • valproate decreases rate of Felbamate elimination • Highly effective in severe refractory cases, but use limited by hepatic and haematological toxicity.
  • 71.
    GABAPENTIN • Mechanism ofaction – • Modulates neurotransmitter release by binding to α2-δ subunit of voltage gated Ca channels. This closes N and P/Q pre-synaptic calcium channels, diminishing excessive neuronal activity and neurotransmitter release • Indications – • Adjunctive therapy or monotherapy of partial or secondary generalized seizures. • also used in Neuropathic Pain, postherpetic neuralgia and diabetic neuropathy. • Dosage: • Significant drug interactions: • Antacid can reduce absorption by abt 20%. • Adverse effects – • Drowsiness (24.4%), dizziness (20.3%), ataxia (17%), headache (15%), tremor, diplopia, nausea, vomiting, non-pitting pedal edema, weight gain • Effective in focal epilepsy but may aggravate generalized epilepsy. • Spectrum of efficacy restricted to partial epilepsies
  • 72.
    LAMOTRIGINE • Mechanism ofaction – • Blockade of voltage dependent sodium and calcium channels. • Indications – • Adjunctive therapy and monotherapy of partial seizures (with or without secondary generalization), other generalized epilepsy syndromes, including Lennox-Gastaut Syndrome • Dosage: • Significant drug interactions: • Serum Lamotrigine levels are increased by Valproic acid as Valproate reduces rate of Lamotrigine elimination • adverse effects – • Dizziness, diplopia, ataxia, blurred vision, somnolence, insomnia, headache, nausea, asthenia, skin rash • Useful drug which can be used as 1st or 2nd line monotherapy, or as adjunctive therapy in treatment of partial seizures and occasionally in generalised epilepsy syndromes. • Main disadvantage is need for slow-dose escalation.
  • 73.
    TOPIRAMATE • Mechanism ofaction – • Blockade of voltage dependent na and ca channels • Potentiation of GABA mediated inhibition at GABA A receptors, • Reduction of excitatory action of glutamate via AMPA receptors, - • Inhibition of carbonic anhydrase. • Indications – • Adjunctive therapy or monotherapy of partial and secondary GTCS. Also useful for Lennox- Gastaut Syndrome and primary • Dosage: • Significant drug interactions: • Serum Topiramate levels are reduced by enzyme inducing AEDs (Phenytoin, carbamazepine, phenobarbital). • Topiramate may increase serum Phenytoin levels. • Adverse effects – • Dizziness, ataxia, somnolence, paraesthesia, tremor, somnolence, cognitive dysfunction, confusion, agitation, amnesia, depression, headache, nausea, diarrhoea, diplopia, weight loss. A very useful drug with relatively broad spectrum efficacy. - Safe in pregnancy. - Main advantage is high responder rates. - Main disadvantage is CNS adverse effects. - Dose reduction required in renal diseases.
  • 74.
    LEVETIRACETAM • Mechanism ofaction – • Binds to Synaptic Vesicle 2A (SV2A) protein. Precise mechanism by which this binding acts is unknown but is likely to involve inhibition of neurotransmitter release from nerve end terminals. • Indications – • First- line and adjunctive therapy of partial-onset seizures. • Adjunctive and, possibly, first line therapy of GTCS and Myoclonic seizures associated with idiopathic generalized epilepsies. • Dosage: • 20-60 mg/kg/day. Tt may be started with 10-20 mg/kg/day and adjusted according to response , by increments of 10-20 mg/kg/day every 2 weeks • Significant drug interactions: • Serum Levetiracetam levels are reduced by enzyme inducing AEDs (Phenytoin, carbamazepine, phenobarbital) by about 20-30 %. • Adverse effects – • Dizziness, ataxia, somnolence (10%), asthenia, infection, nervousness, irritability, behavioural and Psychiatric disorders (12.9% vs 6.2% of placebo patients), suicidal behaviour • Main advantage is Relatively broad spectrum activity, good tolerability, and lack of clinically significant drug interactions. • Main disadvantage is efficacy in some generalized seizure types and epilepsy syndrome unproven. Behavioural and psychiatric adverse effects
  • 75.
    OXCARBAZEPINE • Mechanism ofaction – • Blockade of voltage gated Na channels and N and P type calcium channels. • Indications – • Adjunctive therapy or monotherapy for partial and secondary generalized seizures. • Also useful to treat primary generalized tonic clonic . • Dosage: • 20-60 mg/kg/day. Tt may be started with 10-20mg/kg/day and adjusted according to response , by increments of 10-20 mg/kg/day every 2 weeks • Significant drug interactions: • Serum Oxcarbazepine levels are reduced by enzyme inducing AEDs by promoting its clearance. • Oxcarbazepine may increase the levels of phenytoin and Phenobarbital. • Main advantage is that it is better tolerated and has fewer interactions than carbamazepine. Risk of hepatotoxicity is estimated to be lower than carbamazepine. • Main disadvantage is efficacy spectrum restricted to partial epilepsies. Higher incidence of hyponatremia compared with carbamazepine. • Not indicated for absence, myoclonic and other types of generalized seizures other than tonic-clonic seizures and indeed may exacerbate them.
  • 76.
    ZONISAMIDE • Mechanism ofaction – • Multiple including blockade of voltage • gated Na channels, blockade of T-type calcium channels, potentiation of GABAergic transmission and • inhibition of Carbonic anhydrase. • Indications – • Adjunctive therapy for partial and secondary generalized seizures. • May also be used as adjunctive therapy in primary eneralized seizures. Myoclonic Epilepsies • Dosage: • Significant drug interactions: • Serum Zonisamide levels are reduced by enzyme inducing AEDs. • Administration with food does not reduce the extent but decreases the rate of absorption. • increase in the incidence of renal stones if given with topiramate (CA Inhibitors) • adverse effects – • Agitation, irritability, confusion, depression, anorexia, Weight loss, Nephrolithiasis, skin rashes (including Stevens Jonhnson Syndrome), blood dyscrasias and hypersensitivity reaction. • broad spectrum of Efficacy Main advantage Main disadvantage is CNS adverse effects. • No proven safety in Pregnancy,
  • 77.
    ESLICARBAZEPINE ACETATE • Mechanismof action – • Blockade of voltage gated sodium channels resulting in stabilization of hyper- excitable neuronal membranes. • Indications – • Adjunctive therapy for partial seizures. • Dosage: • Significant drug interactions: • Enzyme inducing AEDs reduce serum Eslicarbazepine levels. Eslicarbazepine acetate decreases the levels of OCPs. • Adverse effects – • Dizziness , blurred vision, headache, nausea, diplopia, nausea, vomiting, visual disturbances • Main advantage is usually well tolerated, once daily dosing • Main disadvantage is limited clinical experience, efficacy spectrum probably restricted to partial epilepsies.
  • 78.
    RETIGABINE • Mechanism ofaction – • Activation of voltage gated neuronal Potassium channels [KCNQ (kv7)], resulting in enhanced M-current, and thereby stabilization of resting membrane potential. • Indications – • Adjunctive therapy for refractory partial-onset seizure. • Dosage: • Significant drug interactions: • Retigabine increases Lamotrigine levels by about 20%. • Enzyme inducing AEDs reduce serum Lacosamide levels by approx 30 %. • Adverse effects – • Dizziness , somnolence, fatigue, confusion, dysarthria, confusion, tremor, urinary hesitancy/retention. • Main advantage is clearly defined dose related efficacy, low interaction potential. • Main disadvantage is need for gradual titration and for frequent dosing, CNS adverse effects
  • 79.
    Perampanel • A highlyselective, non competitive AMPA (a-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid) receptor antagonist. • The mechanism of action • Reduces neuronal hyperexcitability by targeting glutamate activity at postsynaptic AMPA receptors. • Approved as an adjunct therapy for focal-onset seizures and primary generalized tonic-clonic seizures (GTCS) in patients aged 12 years and older • Once-daily dosing and has a half-life of 106 hours. • Common adverse events are dizziness, fatigue, headache and somnolence. Specific adverse effects to monitor are neuropsychiatric events, including aggression, anger, homicidal ideation, hostility, and irritability
  • 80.
    Cannabidiol (CBD) • Reducesneuronal hyperexcitability through a unique multimodal mechanism of action. • It antagonizes G protein-coupled receptor 55 (GPR55) at excitatory synapses. • The inhibition of intracellular calcium release decreases excitatory currents and seizure activity. • CBD desensitizes transient receptor potential vanilloid type 1 (TRPV1) channels The resultant decrease in extracellular calcium influx decreases neurotransmission. • CBD inhibits equilibrative nucleoside transporters (ENT1), reducing adenosine reuptake. The increase in extracellular adenosine reduces hyper excitability and neurotransmission. • NICE guidelines published in December 2019 states that cannabidiol with clobazam is recommended as an option for treating seizures associated with Dravet syndrome and LGS in patients aged 2 years and older,
  • 81.
    Ketogenic Diet andAtkin’s diet • The ketogenic diet (KD) is a stringently controlled high fat and low protein/carbohydrate diet given with/without a restricted fluid intake to maintain ketosis on a long term basis. • It has been shown that it is more efficacious than newer AEDs in controlling refractory seizures • A ‘ketogenic’ ratio of at least 3:1 is usually needed for maintenance of a good state of ketosis and optimal seizure control
  • 82.
    Surgical Remedies Hemispheric epilepsies Developmentaltumors, cortical dysplasias, AVMs Mesial temporal lobe epilepsy caused often by hippocampal sclerosis Drop attacks with injuries respond well to corpus callosotomy
  • 83.
    Take Home Message •Approach a child with seizures systematically • Seizures and epilepsy are clinical diagnoses • Well reported good EEG supports the clinical diagnosis • Use neuroimaging judiciously; avoid CT scans • Treat the patient and NOT the EEG report • Epilepsy treatment is tailor made
  • 84.