RECENT GUIDELINES ON MANAGEMENT OF CHILDHOOD EPILEPSY

Moderator- Dr. Sharja Phuljhele(M.D.)Professor and head –Deptt. Of Paediatrics

PRESENTED BY –DR. YAVNIKA JAIN

ABOUT EPILEPSY A seizure is the manifestation of an abnormal, hypersynchronous

discharge of a population of cortical neurons. It can be a clinical seizure, or it may be subclinical seizure.

The current definition of epilepsy is the tendency to have repeated seizures (at least two) as a consequence of a brain disorder, that is, unprovoked by an acute systemic or brain insult. This definition stresses that the problem is one of brain function, and that the patient has the potential for more seizures. This definition excludes seizures due to exogenous factors.

AMERICAN EPILEPSY SOCIETY 2015

ILAE Classification of Seizures

Seizures

Partial Generalized

Simple Partial

Complex Partial

Secondarily

Generalized

Absence

Myoclonic

Atonic

Tonic

Tonic-ClonicC-Slide 3ILAE – International League Against Epilepsy

Epileptic discharges that occur in the sensory cortex may produce sensory seizures that manifest as hallucinations or illusions.

Motor seizures alter muscle activity. Localized tonic posturing (stiffening) or clonic movements (twitching, jerking) can occur. Abnormal movements may be restricted to one body part or involve gradual spread to adjacent areas on the same side of the body (Jacksonian seizure) or both sides of the body with loss of consciousness (secondarily generalized seizure).

The diverse range of simple partial seizures gives rise to diagnostic challenges.

SIMPLE PARTIAL SEIZURE

COMPLEX PARTIAL SEIZURE

A common misunderstanding is that this requires seizure spread to both sides of the brain. The majority of complex partial seizures originate in the temporal lobe and can affect consciousness while still remaining focal. Automatic movements (automatisms) are common and involve the mouth (e.g., lip smacking, chewing, swallowing), upper extremities (e.g., fumbling, picking), vocalization/verbalization (e.g., grunts, repeating a phrase), or complex acts (e.g., shuffling cards). More dramatic automatisms occasionally occur (e.g., screaming, running, disrobing, pelvic thrusting).

After the seizure, postictal confusion is common, usually lasting less than 15 minutes, although other symptoms, such as fatigue, may persist for hours.

SECONDARY GENERALIZED EPILEPSY 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.

following a secondarily generalized seizure, the patient may have focal weakness (Todd’s paralysis) on the side contralateral to seizure onset.

ABSENCE SEIZURE 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

ATYPICAL ABSENCE SEIZURESBrief 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

PARTIAL SEIZURE

Two main types , depending on whether or not consciousness is fully preserved. Simple partial seizures :consciousness is preserved; the person is alert, can respond to questions or commands, and cant recall.

Complex partial seizures: consciousness is altered or lost; the ability to pay attention or respond to questions or commands is thus impaired or lost. Often, there is no memory of what happened during all or part of the complex partial seizure.

Partial onset seizures may progress to secondarily generalized seizures. Secondarily generalized seizures ultimately involve motor activity on both sides of the body.

MYOCLONIC SEIZURE

Brief, shock-like jerk of a muscle or group of muscles . Differentiate from benign, non epileptic myoclonus (e.g., while falling asleep).

EEG: Generalized 4-6 Hz polyspike-wave discharges. Epileptic myoclonus usually causes bilateral, synchronous jerks most

often affecting the neck, shoulders, upper arms, body, and upper legs. Consciousness does not usually seem to be impaired, although this is

difficult to verify given the brief duration of <1 second.

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

GENERALIZED TONIC CLONIC SEIZURE

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

…EPILEPSY SYNDROMEGrouping of patients that share similar:

Seizure type(s) Age of onset Natural history/Prognosis EEG patterns Genetics Response to treatment

… INTERNATIONAL CLASSIFICATION OF EPILEPSIES AND EPILEPTIC

SYNDROMES 1. Localization-Related (Local, Focal, Partial) Epilepsies and Syndromes 1.1 Idiopathic (with age-related onset) Benign childhood epilepsy with centrotemporal spikes (‘rolandic epilepsy’) Childhood epilepsy with occipital paroxysms 1.2 Symptomatic Chronic progressive epilepsia partialis continua of

childhood (‘Rasmussen’s encephalitis’) Frontal lobe epilepsies Occipital lobe epilepsies Parietal lobe epilepsies Temporal lobe epilepsies 1.3 Cryptogenic

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2. Generalized Epilepsies and Syndromes 2.1 Idiopathic (with age-related onset) Benign neonatal familial convulsions Benign neonatal convulsions Benign myoclonic epilepsy in childhood Childhood absence epilepsy (pyknolepsy) Juvenile absence epilepsy Juvenile myoclonic epilepsy 2.2 Cryptogenic or Symptomatic West syndrome Lennox-Gastaut syndrome 3. Epilepsies and Syndromes Undetermined Whether Focal or Generalized 4. Special Syndromes

Neonatal sizures- Hypoxic ischaemic encephalopathy Intracranial haemorrhage Hypoglycaemia Infection Cerebral dysgenesis HypocalcaemiaInfancy and childhood

Prenatal or birth injury Inborn error of metabolism Congenital malformationChildhood and adolescence Idiopathic/genetic syndrome Trauma

Etiology of Seizures and Epilepsy

…Adolescence and young adult

Head trauma

Drug intoxication and withdrawal*Older adult

StrokeBrain tumorAcute metabolic disturbances*Neurodegenerative

*causes of acute symptomatic seizures, not epilepsy

Idiopathic Partial Epilepsies in Childhood

1.Benign epilepsy with cento-temporal spikes(Benign rolandic epilepsy,BECTS)

This should be considered when a normal school aged child presents with brief and infrequent, partial, nocturnal, hemi-facial, sensory or motor seizures.

An awake-cum- sleep EEG is necessary, as it displays a characteristic pattern of sleep activated runs of centro-temporal spikes or sharp waves.

The syndrome has an excellent prognosis with remission in most cases by the age of 15-16 years.

Guidelines for Diagnosis and Management of Childhood Epilepsy. EXPERT COMMITTEE ON PEDIATRIC EPILEPSY, INDIAN ACADEMY OF PEDIATRICS INDIAN PEDIATRICS VOLUME 46__AUGUST 17, 2009

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2.Panayiotopoulos syndrome (Early-onset childhood epilepsy with occipital paroxysms, CEOPs)

CEOP should be considered when a normal preschool (3-5 yrs) child presents with severe nocturnal vomiting, followed by eye deviation and status epilepticus, usually hemiclonic. This syndrome has an excellent outcome. A later-age Gastaut variant of CEOPS is usually characterized by diurnal simple partial seizures with visual hallucinations or amaurosis and migraine like headaches. This has a variable prognosis and can persist into adult life.

Neuroimaging is considered in cases with an abnormal perinatal history or examination, atypical EEG, or poorly controlled seizures.

In long term therapy, carbamazepine or valproate are preferred.

Idiopathic Generalized Epilepsies

1.Childhood absence epilepsy (Petit-mal, CAE)

This should be suspected in a normal school age child with frequent absence seizures often upto a hundred a day.

An EEG showing a typical pattern characterized by frontally predominant generalized bursts of 3 Hz spike wave complexes with abrupt onset is diagnostic.

There is no role for routine neuroimaging. Valproate and ethosuxsimide followed by lamotrigine and the

benzodiazepines are the drugs of choice. Response to AEDs should be confirmed by repeat EEG with

hyperventilation to check the disappearance of typical EEG pattern. Treatment is for a minimum seizure free period of 2 years with a normal EEG at discontinuation.

… 2.Idiopathic generalized epilepsies of adolescent When a child presents with absence, myoclonic or after 10 years, a

diagnosis of idiopathic generalized epilepsies of adolescent onset is considered. EEG shows generalized paroxysms of spike or polyspikes wave discharges. Photosensitivity is common. Juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE) and epilepsies with only GTC seizures should also be considered in Diagnosis.

JME presents in adolescents with history of early morning predominant upper limb myoclonic jerks leading to the patient dropping objects. This occurs often in sleep-deprived individuals, especially if suddenly awakened. JAE is similar to CAE, though the numbers of absences are much less and the onset is usually later. GTC seizures typically occur on awakening or in the evening.

… Sodium valproate is the most effective drug in most cases of

idiopathic generalized epilepsy.

Carbamazepine and phenytoin may worsen the syndromes. Lifestyle adjustments include avoiding precipitating factors like sleep deprivation and alcohol consumption.

Seizure control is achieved in 80% with monotherapy. Withdrawal of AEDs results in relapse in more than 90%, especially in JME and JAE, and often need low dose lifetime medication.

INVESTIGATIONS IN EPILEPSY Electroencephalography (EEG)- normal EEG does not rule out epilepsy. In the child with uncontrolled epilepsy, a repeat EEG helps in

reclassifying the syndrome. Before AED discontinuation, an EEG aids in predicting risk of

recurrence in most syndromes barring a few e.g. BECTS. In children with unexplained cognitive,neurobehavioral or scholastic

deterioration; an EEG may help in diagnosis of specific disorders like SSPE, or epileptic encephalopathies like electrical status in slow wave sleep (ESES), and nonconvulsive status epilepticus.

How should an EEG be done?

EEG should be recorded 3-4 days after the last seizure to avoid post-ictal slowing from interfering with the interpretation.

A sleep EEG after deprivation should be part of all routine recordings in children above the age of three years.

Minimum activation procedures like hyperventilation and photic stimulation should be used.

Omission of AED prior to EEG recording is not recommended.

Simultaneous video-EEG is useful in differentiating non-epileptic events from true seizures and for pre-surgical evaluation.

NEUROIMAGING MRI is more sensitive than CT and is the modality of choice. MRI

protocol should be adapted to the age of the child and the type of epilepsy syndrome.

CT retains a role in detecting calcification and in acute situations like head trauma, status epilepticus, and epilepsy, where granulomas are a possibility. Neuroimaging is not recommended in benign epilepsies.

High resolution MRI with special techniques is recommended for delineating the epileptogenic zone and the eloquent cortex in pre-surgical evaluation.

Catastrophic Epilepsies in Infancy andEarly Childhood 1. Early myoclonic encephalopathy 2. ohtahara syndrome of infancy 3. epilepsy of infancy with migrating 4. west syndrome 5. Dravet syndrome 6. epilepsy with myoclonic atonic seizure(astatic) {Doose syndrome} 7. Lennox gestaut syndrome 8. Landau Kleffner syndrome 9. epileptic encephalopathy with continuous spike and wave during

sleep (CSWS).

WEST SYNDROME A detailed history of preceding perinatal events (hypoxic-ischemic

encephalopathy, neonatal hypoglycemia, developmental milestones,examination of the skin for stigmata of tuberous sclerosis, head circumference measurement and careful neurologic/developmental examination looking for deficits/delays will help to differentiate cryptogenic vs. symptomatic spasms.

An EEG should be done to confirm the diagnosis, though the characteristic pattern of hypsarrhythmia is not mandatory for diagnosis. Moreover, an experienced electroencephalographer should be available for interpretation.

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Steroids are the drugs of first choice in all cases of West syndrome especially so in cryptogenic WS, except in tuberous sclerosis.

ACTH is preferred over oral steroids. Oral prednisolone is given in doses of 2-4 mg/kg or natural ACTH in

30-40 units/day (3-6 U/kg) for 2 weeks, with rapid taper over the next 2 weeks.

Rapid control of the spasms within 1 month of onset is associated with rapid developmental gains (VPA could be continued after steroids in symptomatic West syndrome).

Vigabatrin is preferred in TS as first choice and in steroid failures in the others (taking into account availability/affordability issues). It should be used for a period of 3-6 months only, due to the fear of visual field defects.

LENNOX GASTAUT SYNDROME Any toddler, who has epileptic drop attacks and is delayed or has

arrest in development, should be considered to have LGS. Usually other types of seizures are also present (like atypical absence and brief tonic seizures in sleep).

MRI is essential. An EEG should be performed to confirm the diagnosis though the

typical slow spike-wave paroxysms are not mandatory for diagnosis. It is mandatory for diagnosis of non-convulsive status epilepticus, which often occurs in LGS and manifests as decreased responsiveness, drooling and regression of milestones lasting hours to days

VPA and CLB should be used initially. LTG or TPM should be added in case of continuing seizures.Ketogenic diet should be used early, if available.It is best to refer such children to a tertiary epilepsy center to manage these complicated patients.

DRAVET’S SYNDROME (SEVERE MYOCLONIC EPILEPSY OF INFANCY) They often present as refractory febrile or afebrile status epilepticus

(SE) which often lasts several hours. Over the next 2-3 years, delayed language development, autistic

features and later, gait difficulties become evident. Myoclonic and absence seizures, often photosensitive usually become prominent after the first year, though they are not mandatory for diagnosis.

VPA, CLB and TPM are drugs most likely to help prevent SE, though a full remission is unlikely to occur. LTG and CBZ regularly worsen these seizures and therefore should be avoided in all febrile seizures in infancy, even those which are clinically focal.

REFRACTORY EPILEPSIES IN OLDER CHILDREN AND ADOLESCENTS

MESIAL TEMPORAL LOBE EPILEPSY- Clinical recognition of mesial temporal lobe epilepsy (MTLE) is

important as it is the most common refractory epilepsy syndrome in the older child/teenager. It is often caused by hippocampal sclerosis, though other etiologies like cortical dysplasia, tumors and vascular malformations may also underlie it. It presents as complex partial seizures with an aura of fear or epigastric sensation followed by unresponsiveness, automatisms and later secondary generalization. The patients have often had febrile seizures (often febrile status epilepticus) in the past. The complex partial seizures present several years later and over time become refractory.

… Sleep deprived EEGs with special electrodes are often needed. High

quality MRIs need to diagnose hippocampal sclerosis and where MTLE is suspected.

In many children, conventional AEDs like CBZ, PHT and newer AEDs like OXZ and TPM are effective for a while in controlling seizures.

A large number become resistant to AEDs and there is a progressive cognitive, behavioural and memory impairment, if the epilepsy remains uncontrolled. Early surgery in the form of anterior temporal lobectomy is significantly more effective than best medical treatment in adults.

EPILEPSIA PARTIALIS CONTINUA Epilepsia partialis continua should be suspected when focal, fairly

constant myoclonic/clonic jerks involve one or more parts of the body (face/limb/ tongue) only unilateraly. In most children, progressive, presumably immune-mediated encephalitis, Rasmussen’s encephalitis underlies this disorder. Over time, a progressive hemiplegia with deterioration in cognition and behaviour is usual, as the epilepsy is resistant to all AEDs.

Investigation should include a MRI which is initially often normal but shows progressive hemiatrophy and unilateral signal changes. EEGs are also helpful though they may be deceptively show absence of abnormalities. Only focal background disturbances may be seen. Till a hemiplegia develops immune therapies like steroids and IVIG can be used.

Treatment is again primarily surgical and a hemispheric resection/disconnection are the procedure that seems to benefit a large number.

The only drawback is that a permanent motor/visual field defect is invariant after a hemispherectomy. Hence, this procedure becomes difficult in children who still have good function of the limbs.

… It is important to recognize rare but important syndromes like the

Landau-Kleffner syndrome (LKS) and Continuous Spike-Wave in Slow-Wave Sleep (CSWS). LKS presents as predominant language deterioration in a previously normal child who may or may not have clinical seizures. Initially the child may stop responding when called and may appear to be deaf; there may be school performance as well as behavior deterioration.

CSWS is a more global disturbance with a frank dementia and autism. Both these syndromes are presumably causally associated with a continuous epileptic discharges in non-REM sleep – electrical status in slow wave sleep (ESES). Hence, any child with or without epilepsy, who has cognitive, language and behavioural deterioration should have an awake and more importantly sleep EEG to establish the diagnosis. Evaluation and management of these complex syndromes need referral to specialized epilepsy centers.

STATUS EPILEPTICUS Status epilepticus (SE): A seizure lasting more than 30 minutes or

recurrent seizures for more than 30 minutes during which the patient does not regain consciousness .

*Operational definition: Generalized, convulsive status epilepticus in adults and older children (>5 years old) refers to >5 min of (i) continuous seizures or (ii) two or more discrete seizures between which there is incomplete recovery of consciousness.

Refractory SE: Seizures persist despite the administration of two appropriate anticonvulsants at acceptable doses, with a minimum duration of status of 60 minutes (by history or on observation).

Super-refractory SE: SE that continues 24 hours or more after the onset of anesthesia, including those cases in which the status epilepticus recurs on the reduction or withdrawal of anesthesia.

Multi-disciplinary Consensus Development Workshop on Management of Status Epilepticus in Children in India’ 2013

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REFRACTORY STATUS EPILEPTICUS EEG monitoring, if available, is important both to monitor for

electroclinical seizures or non-convulsive electrographic seizures, and to titrate therapy and the depth of anesthesia. Additional investigations include a high resolution (3 Tesla) MRI to look for cortical dysplasias, metabolic work-up (blood Tandem mass spectrophotometry and/or blood/urine Gas chromato-graphy mass spectrophotometry) in young children, and work-up for autoimmune encephalitis in patients with de novo status epilepticus associated with fever.

TREATMENT

1. benzodiazipines 2. other anti-epileptic drugs-use wisely 3. topiramate – newer drug 4. midazolam infusion/PROPOFOL??? Doses up to 36µg/kg/min

have been used in previous studies, and may be tried provided it is being used in an ICU setting and appropriate monitoring and management facilities are available. Tapering should be started 24-48 hours after seizure stops at the rate of 1 µg/kg/min, every 3-4 hours.

5. Thiopental sodium with bolus of 3 mg/kg, repeated after 2 min, followed by maintenance (1-5 mg/kg/hr) to control seizures and/or to achieve "suppression-burst" EEG activity (increasing 1 mg/kg/hr every 2 minutes

6. Thiopental usually causes respiratory depression. It can also induce hypotension and heart failure, and inotropic support is frequently needed.

SUPER-REFRACTORY STATUS EPILEPTICUS

Around 15% of all those presenting to hospital in SE develop super-refractory status epilepticus and the mortality is 30-50%.

Therapies for this entity have not been well studied. Treatment modalities depend on the availability of resources, and experience and familiarity of the treating physicians with the various modalities. Other than the previously mentioned drugs; the agents and modalities that have been tried in super-refractory status epilepticus include ketamine, inhalational halogenated anesthetics, magnesium infusion, steroids and immunotherapy, ketogenic diet, hypothermia, electrical and magnetic stimulation therapies, electroconvulsive therapy, and CSF drainage. Emergency neurosurgery may be considered in children in whom a lesion has been detected as the cause of status epilepticus, e.g. cortical dysplasia.

FEBRILE SEIZURE Any prophylaxis of febrile seizures reduces the recurrence of seizures

but does not reduce the risk of future epilepsy. Intermittent prophylaxis with oral clobazam in a dose of 0.75 mg/kg for 2-3 days in 2 divided doses during fever is useful to prevent recurrence. Febrile status, complex and recurrent febrile seizures (>6/year in spite of intermittent prophylaxis) may need EEG, neuroimaging and continuous prophylaxis with AED. Phenobarbitone and valproate may be used in infants and older children respectively, for 1-2 years. Carbamazepine and phenytoin are not useful.

WITHDRAWL OF ANTI-EPILEPTICS ?? New-onset SE: Further treatment decisions should be similar to that

for a First seizure.Acute symptomatic seizures: Further treatment depends on the control of the precipitating event.SE in known epilepsy:• After control of SE for 24 hours, tapering of drugs should be started with ‘last in, first out’ as the guiding principle. • All the AEDs should preferably be stopped during hospital stay and the child discharged on:   –  Augmented dose of the previous AED/s (if levels were sub-therapeutic or prescribed dose was less than maximum  dose); and   –  Introduction of another appropriate AED (either replacement or addition), if previously receiving maximum doses of AED/s.

AEDs- Phenobarbitone – Enhances GABA a receptor mediated synaptic inhibition and antiglutamate

action. can be used as a first line AED in neonatal seizures, in the first two years of life

for partial/GTC seizures and in neonatal and early infantile status epilepticus(SE). Since deleterious cognitive and behavioral side effects remain a concern, it should be avoided In schoolgoing children.

Phenytoin- Prolongs inactive state of sodium channel + pro-gaba + anti glutamate action. Though effective, should not be preferred as a primary AED in newly diagnosed

epilepsy, especially in infancy, as levels fluctuate frequently in infants, making monitoring of drug levels imperative, and in adolescent girls as cosmetic side effects may be unacceptable. Maintenance dosages in older children are between 5-6 mg/kg given in one or two divided doses, but infants may need upto 15-18 mg/ kg in 3-4 divided doses.

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Valproate- Pro GABA ,anti glutamate , prolongs inactive state of sodium channels and weak

attenuation of Ca mediated T current. can be the drug of choice for most children with newly diagnosed epilepsy, like idiopathic generalized epilepsy (CAE, JAE, BMEI, and JME), epilepsies with prominent myoclonic seizures or with multiple seizure types, and photosensitive epilepsies.

In adolescent girls or obese patients, one may not use it as first line agent. Hair loss may be reduced by use of supplemental biotin. It could be used in partial epilepsies in infants where carbamazepine might precipitate generalized seizures and in refractory status epilepticus.

The dose averages between 10-40 mg/kg/day. Twice-a-day dosing is preferred with extended release preparations, except in syrup (3 times a day). Parents should be counseled regarding danger symptoms and signs of hepatitis, like nausea, vomiting, drowsiness etc, especially in children below the age of 2 years, those on polytherapy and those with associated IEM, necessitating routine monitoring of LFT. Enzyme elevation upto twice normal or borderline elevation of ammonia can be disregarded when asymptomatic. The drug must be stopped immediately in all symptomatic patients irrespective of enzyme levels. In case the cause of the hepatitis becomes clear e.g. hepatitis A confirmed by serology, then valproate could be restarted after the hepatitis has resolved. In cryptogenic hepatitis it is best avoided. Carnitine supplements are not routinely recommended.

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Carbamazepine- Prolongs inactive state of sodium channels, modifies maximal electroshock

seizures raises threshold. It is the drug of first choice for all newly diagnosed partial epilepsies, after the

age of 2 years. The dose varies between 10-30 mg/kg in the form of twice day dosing and preferably given as slow release preparations, if syrups are used they should be given three times a day. Carbamazepine may induce or exacerbate generalized seizures like infantile spasms, myoclonic, tonic and absence seizures in the younger child. Paradoxically, it may exacerbate partial seizures as well, in benign partial epilepsies. It may worsen the EEG with deterioration in cognition, behavior and language & can rarely precipitate electrical status in slow wave sleep (ESES). Parents should be informed about the common side effects like appearance of new seizures, deterioration of school performance or appearance of rash (Steven’s) Johnson’s and Drug Rash Eosinophilia and Systemic Symptoms- DRESS syndrome shared with phenytoin and pheno-barbitone) which should be reported immediately. A routine hematological monitoring is not recommended.

… Oxcarbazepine- converts to glucoronide conjugated product and not

oxidized. Can be used as monotherapy in newly diagnosed partial epilepsy for

children above 4 years of age, if affordable and available. It can be used for add-on therapy in refractory partial and secondary generalized epilepsy. Start with a dose of 10 mg/kg; titrated upwards weekly, guided by seizure control, to a maximum of 40 mg/kg. Though once daily preparations are marketed, it is prudent to give this drug in two divided doses. An abrupt switchover from CBZ to OXZ can be done in a dose ratio of 2:3. No routine monitoring of drug levels, blood counts or sodium is recommended, unless symptomatic (vomiting, drowsiness or increased seizures)

… Lamotrigine – broader spectrum , CBZ like action+prolongs sodium inactive

state,directly inhibiting sodium channels(preventing release of aspartate and glutamate).

Monotherapy in newly diagnosed generalized epilepsy (absence and myoclonic) and in other partial/generalized epilepsies, and in specific epilepsy syndromes like idiopathic generalized epilepsy in teenage years, especially girls (as first choice). Occasionally, myoclonic jerks maybe paradoxically worsened by lamotrigine, especially in JME. Add-on in refractory generalized epilepsies like absence, tonic and tonic-clonic and syndromes like LGS and in refractory partial epilepsies.

The dose should initially be 0.5 mg/kg (alone), 0.2 mg/kg (with VPA), and 0.6 mg/kg (with phenobarbitone, phenytoin, carbamazepine); it should be doubled every 2 weeks to a maximum of 15mg/kg (alone) and 5mg/kg/day (with VPA) and higher when used with enzyme inducers. LTG has to be titrated slowly to prevent rashes and Stevens Johnson syndrome.

… Topiramate- Hyperpolarizes the membrane,phenytoin like prolongation of inactive

state of sodium channels, phenobarb like pro GABA action and antagonist of glutamate.

It can be used as a second line add-on agent in refractory partial and generalized epilepsies as well as Lennox Gastaut syndrome. It maybe particularly useful in certain syndromes like infantile spasms and Dravet’s syndrome. At present, its use as first line monotherapy in newly diagnosed epilepsy is not recommended because of a significant adverse effect profile.It should be started at a dose of 0.5-1 mg/kg in bid doses, escalated weekly or biweekly, upto maximum of 5-10mg/kg; Higher doses (10-30 mg/kg) and rapid escalation (every 3 days) are considered in special situations (infantile spasms, status epilepticus); however, there could be a higher incidence of adverse events with high doses.

Clinical monitoring for adverse effects like weight loss, eye symptoms like blurring, redness,watering and eye pain (glaucoma/myopia), metabolic acidosis and oligohydrosis is necessary in all cases. Decreased appetite and weight loss are expected and should be communicated to the caregivers. Cognitive adverse effects can be minimized by converting to topiramate monotherapy, if possible. Hydration should be maintained and calcium supplements should be avoided to minimize risk of renal stones.

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Levatiracetam-

It should be used only as an add-on drug to refractory partial and some generalized epilepsies like,refractory absence or progressive myoclonic epilepsies. It is not recommended to be used as a first-line agent in newly diagnosed epilepsies,though recent data support a role in the idiopathic generalized epilepsies of adolescents (JME etc). Behavioral adverse effects like aggression are the most common adverse effects, rarely a paradoxical increase in seizure frequency may occur and this should be monitored carefully. The usual effective dose is between 20-60 mg kg /day. One can start at 20 mg/kg in two doses and increase every 1-2 weeks till 60 mg/kg/day.

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Tiagabine- Potentiates GABA mediated neuronal inhibition. As add-on in refractory partial seizures. It is not recommended as

monotherapy in children with newly diagnosed epilepsy. NCSE (non convulsive status epilepticus) can occur in about 8% of patients and should be carefully excluded in children whose seizures/mental status deteriorate on treatment. It is used in an initial daily dose 0.1 mg/kg TID; increased weekly by 0.1 mg/kg; maximum daily dose 0.4 and 0.7 mg/kg (uninduced and induced, respectively). In children over 12 years, it can be initiated at 4 mg/day; total daily dose increased by 4 mg in week 2 (divided doses); then increased by 4 to 8 mg/day (divided doses) each week until clinical response is achieved or to a maximum daily dose of 32 mg/d is reached.

LATEST DRUGS- ZONISAMIDE-Focal seizures with or without GTCS. Used as adjunct in LGS and JME.Started at 1-2 mg /kg/day to maintenance of 4-8 mg/kg/day.S/E Nephrolithiasis and oligohydrosis. LACOSAMIDE-Paediatric experience is limited .Used in children >16 yrs with refractory focal seizures.S/E dizziness, headache,diplopia. RUFINAMIDE-Add-on therapy for LGS .Start with 200mg /day in children <30 kg , upto maximum of 1000mg/day.( if used with valproate then 400 mg/day)Not use in those with short QTc syndrome. STIRIPENTOL- Used in GTCS with Dravets syndrome

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Guidelines for Diagnosis and Management of Childhood Epilepsy.Neurology chapter of IAP-2014. 

… DOSES AND SIDE EFFECTS OF COMMON ANTIEPILEPTIC DRUGS- Phenobarbitone 3-8 mg/kg Hyperactivity, academic deterioration, reversal of

sleep cycles,megaloblastic anaemia,osteomalacia Phenytoin 5-15 mg/kg Poor seizure control due to fluctuating drug levels,

cosmetic side effects,hirsutism, ataxia Valparin 10-60 mg/kg Nausea, vomiting, loss of appetite, weight gain, irregular

menstruation, alopecia, hepatotoxicity,somnolence,teratogenicity Carbamazepine 10-30 mg/kg Drug rash, worsening seizures,dizziness, vertigo,

rarely worsening school performance Oxcarbazepine 20-45 mg/kg Somnolence, vomiting (hyponatremia), seizure

exacerbation Lamotrigine 0.2- 15 mg/kg Drug rash, Steven-Johnson syndrome Clobazam 0.4-1.2 mg/kg Behaviour changes, aggression, sleep disturbances,

constipation, weight gain Topiramate 3-9 mg/kg Cognitive/language deterioration, fever, acidosis in

infancy Levateracetam 15-45 mg/kg Behaviour changes Tiagabine 0.5-2 mg/kg Somnolence, Seizure exacerbation

DIET Ketogenic Diet in Epilepsy - 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 and is more cost effective. It can be used with both non-vegetarian and vegetarian diets at any age and for all types of Seizures. It has significant improvements in hyperactivity and aggression in almost all patients. Hence, it should be tried in all children above the age of 1 year with drug-resistant epilepsy, especially those who are not a surgical candidates or where surgery cannot be performed due to availability/affordability issues. Referral to centers providing the KD should be considered once adequate trials of three AEDs have failed, suggestive of pharmaco-resistant epilepsy. Adverse effects include GI disturbances, acidosis, increased susceptibility to infections, drowsiness, weight loss, nutritional deficiencies and rarely, renal calculi and pancreatitis. Most of these occur early in the diet and should be carefully monitored. The diet should be considered a failure if there is no benefit in 3-6 months and it should be discontinued after this time. In responders, it should be continued for 2-3 year after which it is gradually tapered.

The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial Lancet Neurol 2008; 7: 500–06 Published Online May 3, 2008

Elizabeth G Neal, Hannah Chaff e, Ruby H Schwartz, Margaret S Lawson, Nicole Edwards, Geogianna Fitzsimmons, Andrea Whitney,

SURGERY Ideal surgically remediable syndromes include: • Hemispheric epilepsies with pre-existing contralateral

hemiplegias/visual field defects caused by large unilateral gliotic lesions/atrophy, Rasmussen’s encephalitis, hemispheric dysplasias etc, where hemispherectomy/hemispherotomies could offer a possible surgical cure.

Discrete lesions without involvement of functional motor, visual and language cortex,where a lesionectomy will often result in a complete cure. Common lesions would include developmental tumors, cortical dysplasias, AVMs etc. Sometimes lesions like large dysplasias/infarcts may need lobectomies/multilobar resections.

• Mesial temporal lobe epilepsy caused often by hippocampal sclerosis is not uncommon in teenagers and is amenable to an anterior temporal lobectomy.

• Drop attacks with injuries respond well to corpus callosotomy and should be offered as a palliative procedure.

REFERENCES- 1 .Guidelines for Diagnosis and Management of Childhood Epilepsy. EXPERT COMMITTEE ON PEDIATRIC EPILEPSY, INDIAN ACADEMY OF PEDIATRICS INDIAN PEDIATRICS VOLUME 46__AUGUST 17, 2009  2. Guidelines for Diagnosis and Management of Childhood Epilepsy.Neurology chapter of IAP-2014.  3. Multi-disciplinary Consensus Development Workshop on Management of

Status Epilepticus in Children in India’ 2013.  4. The ketogenic diet for the treatment of childhood epilepsy: a

randomised controlled trial Lancet Neurol 2008; 7: 500–06 Published Online May 3, 2008

Elizabeth G Neal, Hannah Chaff e, Ruby H Schwartz, Margaret S Lawson, Nicole Edwards, Geogianna Fitzsimmons, Andrea Whitney,