Epilepsy and its management (ppt)
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Transcript of Epilepsy and its management (ppt)
Epilepsy and children By
Dr.Shahnawaz M.K Dal M.B.B.S, D.P.M
Consultant Neuropsychiatrist Sir Cowasjee Institute of Psychiatry Hyderabad
M.K Hospital Hyderabad [email protected]
EPILEPSY
Epilepsy & its management
What is epilepsy ?
An epileptic seizure is a transient occurrence of signs
and or symptoms due to abnormal excessive or
synchronous neuronal activity in the brain.
Epilepsy is a disorder of the brain characterized by an
enduring predisposition to generate epileptic seizures and by the neurobiologic,
cognitive, psychological, and social consequences of this
condition.
Facts about epilepsy
At least two animals still have epilepsy for this reason:
Mexican Waltzing Mouse
Papio Papio baboon
History
The word ‘EPILEPSY’ derived from Greek words meaning “ To
seize upon ” or “Taking held of ”.
In 1870,British neurologist
HUGHLINGS JACKSON defined word EPILEPSY
“An excessive & disorderly discharge of
cerebral nervous tissue on muscles.”
This discharge may be in the form of loss of
consciousness, altered psychological
functions, disturbance of sensations,
convulsive movements or some combination
there of.
So the terminology ‘CONVULSION’ is not
proper as it only involves intense
paroxysm of involuntary muscle
contractions which is improper because this disorder may involve only alteration of the
sensorium or consciousness.
So the SEIZURE is the proper terminology for
that.
Burden of Epilepsy
Persistent stigma
Cognitive problems
Psychiatric disturbances
Long term effects of
AEDs
Low quality of life
Accidents
Sudden death
The goals of the treatment
Seizure freedom
Keep the patient safe
Keep the patient functional
Keep the patient autonomous
Seizure control and the adverse effects are pharmacodynamic measures of a drug effect on the body.
A seizure is a paroxysmal event due to excessive , hyper synchronous , abnormal discharge from the aggregate of the central nervous system.
Definitions
A sudden, brief disruption of the normal functioning of neurons in the brain
A neurological condition causing the tendency for repeated seizures of primary cerebral origin
Epilepsy is not contagious, it is not a mental illness or a cognitive disability.
“Paroxysmal excessive neuronal discharge from the cortical or sub-cortical areas”
CLASSIFICATION
Classification of epilepsy are based on various points….
- Idiopathic(primary) or symptomatic(secondary)
- Generalized or focal
- Isolated ,cyclic or repetitive
GASTAUT in 1970 has refined a definition of epilepsy with the help of ILAE(international league against epilepsy)
By this classification epilepsy has been broadly classified in two major groups based on EEG features & it is accepted world wide.
EPILEPSY:PREVELNCE • There are over 50 million sufferers in the world today, 85% of whom live in
developing countries.1
• At least 50% of cases begin at childhood or adolescence.1
• High prevalence 3.38/1000 was found in children from Government run educational institutions.2
05/01/2023
BARRIERS TO EDUCATION• Embarrassment about having seizures in front of peers can lead to children feeling uncomfortable in the school environment.
• Stigma – feelings of being different to peers – may lead to emotional problems, worry, stress and anxiety.
• Bullying and reluctance to attend school as a result can lead to school refusal.
• Frustration concerning the inability of school staff to understand epilepsy can impact on some young people.
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BARRIERS TO EDUCATION• Impact on self-esteem through negative school experiences can lead to loss of
confidence and self-doubt.
• Fear of seizures can impact on willingness to take part in activities.
• Stressful experiences at school can trigger seizures.
• Fear of Sudden Unexpected Death in Epilepsy (SUDEP) can have a negative impact
05/01/2023
Epilepsy and Related Conditions
• One of the most prominent cognitive changes that occurs in people • with epilepsy is a memory problem (Zemen et al. 2012)
• Epilepsy may be impacting on sleep if children are experiencing seizure activity at night and this may lead to tiredness during the day and impact on learning.
• Anti-epileptic drugs (AEDs) and side effects may be impacting on learning.
• Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) will be impacting on some of the pediatric epilepsy population.
• Anxiety and depression will be impacting on some of the paediatric epilepsy population.
05/01/2023
Types of Epilepsy
Two major categories, namely
1.partial 2. generalised
seizures.
Partial seizures
Epilepsy - Pathogenesis
A. Result of complex genetic mutations and environmental factors can cause
• 1. Abnormal brain wiring AND/OR• 2. Chemical (neurotransmitter) imbalances AND/OR• 3. Abnormal connections made when attempting to repair an injury
B. Hypersensitive neurons may exhibit a sudden or violent depolarization
• 1. epileptogenic (able to cause epilepsy)• 2. Easily activated by hyperthermia, • hypoxia, hypoglycemia, hyponatremia,
sensory stimulation, certain sleep phases
Clinical Manifestations
Often manifests as strange
sensations, emotions & behaviors (including
convulsions)
Many may experience the same seizure events over
and over, while some have many different
types of seizures that cause different
symptoms each time.
Patients should be evaluated
thoroughly after an initial seizure
(complete history)
The type of seizure a person has depends on
a variety of things
The area of the brain affected
Underlying cause of
seizure• Partial or generalized• Time of day of the
event• Occurred during
wakefulness or sleep
Known triggers• flickering
light ,severe sleep deprivation
Tx
Medications used to treat patients with epilepsy are called anticonvulsants.
These drugs each have a different mechanism of action, but all serve to reduce the frequency of epileptic seizures. Monotherapy, treatment with a single agent, is the goal. Many seizures will stop without pharmacological intervention.
Status epilepticus & febrile convulsions.
Status epilepticus is a life-
threatening condition in which seizure activity is
uninterrupted.
Febrile convulsion is associated with temperatures101 in a child under age of 6 years .
PARTIAL SEIZURES
• Seizures that initially affect one specific area in one hemisphere of the brain
• May or may not cause an alteration of consciousness
• Symptoms can include muscle twitching, repetitive motions, and the appearance of “daydreaming”
• Partial seizures can become generalized seizures
DEFINING DIFFERENT SEIZURE TYPES
GENERALIZED SEIZURES
• Seizures that affect both hemispheres of the brain
• Result in a loss of consciousness• Symptoms can include blank stares,
falling to the floor, sudden muscle jerks, and repetitive stiffening and relaxing of muscles
Simple Partial Seizure
Rhythmic movements - isolated twitching of arms, face, legs
Sensory symptoms - tingling, weakness, sounds, smells, tastes , feeling of upset stomach, visual distortions
Psychic symptoms - déjà vu, hallucinations, feelings of fear or anxiety
Usually last less than one minute
May precede a generalized seizure
Difference between
SIMPLE PARTIAL SEIZURES
Complex Partial Seizure
Characterized by altered awareness
Confusion, inability to respond
Automatic, purposeless behaviors such as picking at clothes, chewing or mumbling.
Emotional outbursts
May be confused with:Drunkenness or drug use
Willful belligerence, aggressiveness
COMPLEX PARTIAL SEIZURES
Myoclonus A single abrupt shock like extensor movement of a limb.
Petit Mal Used to describe absence seizures as well as atypical absence.
Tonic Sustained contraction of one or more muscle groups, independent of position (i.e. can be flexed, extended, or opisthotonic).
Aura A generic term for a warning. A colloquial term for simplepartial seizure.
Convulsion Tonic, clonic or tonic-clonic seizure
Generalized Seizures INTERNATIONAL CLASSIFICATION OF EPILEPTIC SEIZURES (abridged version)
Absence seizures
Atypical absence
Myoclonic seizures,
Myoclonic jerks (simple or multiple)
Clonic seizures
Tonic seizures
Tonic-clonic seizures
Atonic seizures (astatic)
GENERALIZED TONIC- CLONIC SEIZURE
Grand mal epilepsy Petit mal epilepsy
Myoclonic seizure Atonic seizure
Status epilepticus Febrile convulsions
Between
Seizures:
• Normal
Appearance
During Seizure:
• Vacant stare • Eyes roll upward• Lack of response
ABSENCE SEIZURE
Includes all seizures that cannot be classified because of inadequate or incomplete data and some that defy classification in described categories. This includes some neonatal seizures, e.g., rhythmic eye movements, chewing, and swimming movements.
UNCLASSIFIED EPILEPTIC SEIZURES
TREATMENT PRIORITIES
No AEDs until diagnosis is confirmed
If uncertainty then period of observation will clarify the epilepsy syndrome
Two seizures
May be started after single seizure in certain circumstances
What Is the Difference Between Epilepsy & Seizures?
A seizure is a symptom of epilepsy
The Brain Is the Source of Epilepsy
Classifying Epilepsy and Seizures
Seizure types:
•Partial Generalized
• Simple Absence • Complex
Consciousnessis maintained
Consciousnessis lost or impaired
Altered awareness
Characterized bymuscle contractionswith or without lossof consciousness
Everything you do, you do with your brain!
Different parts have different functions, and different seizures!
Seizure Triggers
Missed medication (#1 reason)
Stress, anxietyHormonal changes, Menses
DehydrationLack of sleep, extreme fatigue
PhotosensitivityIllicit Drug, alcohol use
Certain Medications
Fever in Some Children
Treatment Goals in Epilepsy
Help person with epilepsy lead full and productive life
Tailor treatment to needs of individuals/special populations :• Women, Children, Elderly,
Hepatic or renal failure and other diseases
What if not treated?
Seizures can be potentially life threatening with brain failure, heart and lung failure, trauma, accidents
Sudden Unexpected Death in Epilepsy (SUDEP)
Even subtle seizures can cause small damage in brain
Long Term problems: fall in IQ, depression, suicide, Social Problems, Quality of Life
Considerations in Epilepsy Management
Age andGender
Seizure Frequency
Underlying Pathology
Comorbidities
Medication Side Effects
Syndrome vs.
Seizure Type
Factors That Affect the Choice of Drug
Seizure type/
Epilepsy syndrome
Side effects & safety
Patient age
Ease of Use
Lifestyle
Age, Sex, Childbearing potential
Other medications
New AEDs offer
Alternative as an add-on
Alternative in case of adverse
effects
Less AED-AED interactions
Less drug-drug interactions in
specific conditions
Better tolerability
Consistent use
Inadequate dosage or ineffective medication
Drug factors
Disease
Factors That Influence Response to Medication
History of Antiepileptic Drug Therapy
1857 - Bromides
1912 - Phenobarbitone
1937 - Phenytoin
1944 - Trimethadione
1954 - Primidone
1960 - Ethosuximide
History of AED therapy
1974 – Carbamazepine
1975 - Clonazepam
1978 - Valproate
1990 - Oxcarbazepine
1993 - Felbamate, Gabapentin
1995 – Lamotrigine, Levetiracetam
1997 - Topiramate, Tiagabine
Choice of AED
syndro
me
age
Life style
comorbidity
Associa
ted drugs
Adverse effectstolerability
Efficacy
A
EDph
arm
acok
in
etic
gender
interactions
cost
Correct diagnosis of the type of epilepsy influences treatment, prognosis and genetic counseling.
One best drug to fit the fit, fit the patient; Sequential monotherapy
Use the least expensive AED (all things being equal, like efficacy).
Prefer AEDs which can be taken od over bid / tid.
AEDs almost never need qid dosing
Start with one AED and push the dose to clinical toxicity or seizure control.
Withdraw AEDs that are not effective.
Never have a patient on more than three (3) AED's.
Principles of AED Selection…cont.
Principles of AED Selection… cont.
Don't use combination medications (e.g., phenytoin with phenobarbital).
No proof that multiple AEDs are synergistic in the treatment of epilepsy.
Polypharmacy is expensive, increases side effects and increases the complexity of adjusting AEDs in the refractory patient.
Antiepileptic drug (AED) - Limitations
A drug which decreases the frequency and /or severity of seizures in people with epilepsy.
Treats the symptom of seizures, not the underlying epileptic condition.
Improves quality of life by minimizing seizures.
Seizure freedom after failure with first AED (Brodie 2000)
Seizure ManagementPharmacologic Treatment
Partial seizures
• Oxcarbazepine• Carbamazepine• Phenytoin• Phenobarbital• Levetiracetam• Lamotrigine• Topiramate• Lacosamide• Zonisamide
Absence seizures
• Ethosuaximide• Valproic acid• Lamotrigine
Seizure ManagementPharmacologic Treatment
Tonic-Clonic Seizures
• Phenytoin• Valproic acid• Carbamazepine• Topiramate• Levetiracetam• Lamotrigine• Zonisamide
Myoclonic and Atonic Seizures
• Clonazepam• Lamotrigine• Levetiracetam• Infantile Spasms• ACTH• Topamax• Zonisamide• Valproic acid
Antiepileptic drugs – “newer
drugs” since 1990
•Felbamate•Gabapentin•Lamotrigine•Topiramate•Vigabatrin•Oxcarbazepine •Zonisamide•Leveteracetam•Pregabalin•Rufinamide•Lacosamide
Choosing the right treatment; balancing efficacy and tolerability
New AEDs offer
Alternative as an add-on
Alternative in case of adverse
effects
Less AED-AED interactions
Less drug-drug interactions in
specific conditions
Better tolerability
Broad Spectrum anti epileptic, used to treat refractory epilepsy
Levetiracetam:
TRADITIONAL ANTI-EPILEPTIC CONCERNS
• Memory impairment & Impaired attention is associated with traditional Anti-Epileptics.
• Liver failure resulting in death has occurred in patients receiving Divalproex Sodium.
• laboratory monitoring needed /LFTs Requires
05/01/2023
05/01/2023
An Ideal Anti-epileptic Drug
• Broad spectrum of efficacy• Goal of Epilepsy Management - Seizure freedom• Sustained efficacy• Optimal therapy with no known clinically
significant drug interactions• Improved quality of life• Dosage convenience
05/01/2023
1. Levetiracetam is a new antiepileptic drug, structurally and mechanistically dissimilar to other marketed antiepileptic drugs.
2. Levetiracetam is an anticonvulsant medication used to treat epilepsy. It is the S-enantiomer of etiracetam, structurally similar to the prototypical nootropic drug piracetam.
3. It is effective in reducing partial seizures in patients with epilepsy, both as adjunctive treatment and as monotherapy.
4. Having favorable pharmacokinetic characteristics (good bioavailability, linear pharmacokinetics, insignificant protein binding, lack of hepatic metabolism, and rapid achievement of steady-state concentrations) and a low potential for drug interaction.
05/01/2023
MECHANISM OF ACTION
• The exact mechanism by which Levetiracetam acts to treatepilepsy is unknown. However, the drug binds to a synaptic vesicle protein, , which is believed to impede nerve conduction across synapses.
• appear to be important for the availability of calcium-dependent neurotransmitter vesicles ready to release their content. The lack of results in decreased action potential-dependent neurotransmission, while action potential-independent neurotransmission remains normal.
05/01/2023
05/01/2023
INDICATIONS
• Monotherapy in the treatment of partial onset seizures with or without secondary generalization in patients from 16 years of age with newly diagnosed epilepsy.
• Adjunctive therapy in the treatment of partial onset seizures with or without secondary generalization in adults and children from 4 years of age with epilepsy.
• Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents from 12 years of age.
05/01/2023
Dosage
EPICETAM-Features• Broad spectrum of potential efficacy
• No hepatic induction
• Well tolerated in most; good cognitive profile
• Excellent safety profile
• No laboratory monitoring needed
• Levetiracetam pharmacology• LEV is rapidly and almost completely absorbed after oral
intake, with peak plasma concentrations approximately one hour after oral administration. Food reduces the peak plasma concentration by 20% and delays it by 1.5 hours, but does not reduce LEV bioavailability (Patsalos 2000, 2003). There is a linear relationship between LEV dose and LEV serum level over a dose range of 500–5000 mg (Radtke 2001). LEV protein binding, at less than 10%, is not clinically relevant. LEV metabolism is not dependent on the liver cytochrome P450 enzyme system. LEV is predominantly excreted unchanged through the kidneys, with only about 27% metabolized.
Mechanism of action
• The exact mechanism by which levetiracetam acts to treat epilepsy is unknown. However, the drug binds to a synaptic vesicle glycoprotein, and inhibits presynaptic calcium channels reducing neurotransmitter release and acting as a neuromodulator. This is believed to impede impulse conduction across synapses
Lamotrigine
Oxcarbazepine
Topiramate
Levetiracetam
Licensed to Monotherapy
ILAE Treatment Guideline (Glauser T, et al.2006 ) NICE (National Institue for Clinical Excellence 2004) guidance on newer drugs for epilepsy in adults SIGN (Scottish Intercollegiate Guideline Network, 2005) SANAD (standard and new antiepileptic drug trial (Marson et al.2007) BESET (Belgian Study on Epilepsy treatment, Legros B, et al. 2007))
SIGN(Scottish Intercollegiate Guideline Network)
All AEDs are equivalent in
new onset epilepsy
First drugs to introduce in new onset epilepsy is
standart AEDs and LTG, OXC
Cosmetic side effects• Hirsutismus Alopecia • Gingiva hyperplasia Coarse face
Reproductive health• Hyperandrogenism Ovulatory disorders
• PCOS Sperm quality, number
Sexual dysfunction• 20-30% W, 50% M; Reduced libido• Anorgasmia
Bone health
Thyroid functions • total, free thyroxine↓
Peripheral neuropathies
Cerebellar atrophy
CBZ VPA PB ESM PHT
Somnolence *
GIS * * **
Liver *
Depression * * *
Blood * * * * *
Cognition * ** *
Osteoporosis (*) (*) * *
Side effects-I
Side effects-II
LTG OXC TPM LEV GBP PGB
Somnolence * ** * * *
GIS * * **Liver
Blood
Cognitive *Osteoporosis
Depression
Engel J, Pedley TA, Epilepsy, 2008
Idiosyncratic side effects
Vigabatrin
Felbamate
Lamotrigine
Topiramate
Topiramate
Oxcarbazepine
Visual field defects
Aplastic anemia
Rash Renal stones
Glaucoma
Hyponatremia
Weight and AEDs
Weight gain Weight loss No effect
VPA
GBP
PGB
VGB
TPM
ZNS
FBM
OXC
LTG
PHT
LEV*
Enzyme inducers vs non-inducer AEDs
Carbamazepine
Phenytoin
Phenobarbital
Primidone
Felbamate
Lamotrigine
Oxcarbazepine
Topiramate
Ethosuximide
Gabapentin
Levetiracetam
Pregabalin
Tiagabin
Valproat*
Vigabatrin
Zonisamide
Narrow-spectrum inducers Non-inducersInducers
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