Download as PDF, PPTX
![AED Common AEs Severe AEs
LCS
Insomnia, somnolence, depression, suicidal ideation,
behavioural problems, blurred vision, tics, nausea,
haematological abnormalities.
No
PER
Dizziness, nausea, somnolence, fatigue, irritability,
headachea
No
RTG
Dizziness, somnolence, headache, fatigue, confusional
state, dysarthria, ataxia, blurred vision, tremor, nausea,
urinary tract infectionsa [95]
Suicidal ideationa [95]
RUF
Ashenia, somnolence, dizziness, diplopia, headache,
nausea, vomiting, anorexia, rash
No
STM Somnolence, vomiting, restlessness, anorexia No
STP
Insomnia, somnolence, aphasia, dysarthria, behavioural
problems, ataxia, tremor, diplopia, headache, abdominal No
Considerations in Choosing AEDs](https://image.slidesharecdn.com/epilepsyoverview-181221132203/75/Epilepsy-overview-140-2048.jpg)
Uploaded byAmr Hassan
Epilepsy overview
The document presents an overview of epilepsy, including its basic concepts, classification, diagnosis, and treatment strategies. It outlines the definitions and processes involved in epileptogenesis, statistics on incidence and prevalence, as well as diagnostic criteria to distinguish between epileptic and non-epileptic seizures. Additionally, it highlights the importance of various diagnostic tools, such as EEG and neuroimaging, in identifying seizure types and determining appropriate therapeutic approaches.
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Epilepsy overview
- 1. Amr Hassan, MD,FEBN Associateprofessor of Neurology Cairo University EPILEPSY OVERVIEW
- 2. AGENDA • Basic conceptsof epilepsy • Epileptogenesis • Classification of Epilepsy • Diagnosis of Epilepsy • Treatment options and strategies
- 3.
- 4. AGENDA • Basic conceptsof epilepsy • Epileptogenesis • Classification of Epilepsy • Diagnosis of Epilepsy • Treatment options and strategies
- 5. • Seizure: theclinical manifestation of an abnormal, excessive excitation and synchronization of a population of cortical neurons. • Epilepsy: recurrent seizures (two or more) which are not provoked by systemic or acute neurologic insults. American Epilepsy Society 2010 Definition of epilepsy
- 6. American Epilepsy Society2010 Epidemiology of epilepsy • Seizures • Incidence: 80/100,000 per year • Lifetime incidence: 9% (1/3 febrile convulsions) • Epilepsy • Incidence: 45/100,000 per year • Point prevalence: 0.5-1% • Cumulative lifetime incidence: 3%
- 7. Etiologies of theepilepsies
- 8. Unknown 15.5% Infection 2.5% Degenerative3.5% Cancer 4.1% Head Injury 5.5% Congenital Malformations 8.0% Stroke 10.9% Idiopathic (Genetic) Epilepsies (~50%) Symptomatic (Acquired) Epilepsies (~50%) Hauser Etiologies of the epilepsies
- 9. AGENDA • Basic conceptsof epilepsy • Epileptogenesis • Classification of Epilepsy • Diagnosis of Epilepsy • Treatment options and strategies
- 10. • Basic conceptsof EPILEPTOGENESIS • Recent developments in our understanding of the molecular aspects of epileptogenesis. • Current status in the development of ANTI- EPILEPTOGENESIS treatments. Epileptogenesis
- 11. Definitions • Epileptogenesis: sequenceof events that converts a normal neuronal network into a hyperexcitable network • Epileptogenesis: is the process by which a brain network that was previously normal is functionally altered toward increased seizure susceptibility, thus having an enhanced probability to generate spontaneous recurrent seizures (SRSs) (Dudek and Staley 2012; Goldstein and Coulter 2013).
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- 18. New definition Epileptogenesis: refersto the development and extension of tissue capable of generating SRSs,resulting in (1) Development of an epileptic condition, and (2) Progression of the epilepsy after it is established.
- 19. “Seizures BEGET Seizures” WilliamRichard Gowers 1845-1915
- 20. Secondary epileptogenesis • Secondaryepileptogenesis area becomes epileptogenic because of the influence of epileptogenic activity in a primary epileptogenic area, which is separated from it by at least one synapse. • A mirror focus is a type of secondary epileptogenesis which the secondary epileptogenic zone is located in a contralateral homotopic area with regard to the primary epileptogenic zone. • Secondary epileptogenesis is likely due to kindling.
- 21.
- 22. Normal CNS Function Excitation Inhibition glutamate, aspartateGABA Modified from White, 2001
- 23. Hyperexcitability Excitation Inhibition GABA Modified from White,2001 American Epilepsy Society 2008 Excitatory post synaptic potentials (EPSPS) Inhibitory post synaptic potentials (IPSPS) Changes in voltage gated ion channels Alteration of local ion concentrations Molecular, Anatomical or Circuit level alterations
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- 25. Inherited Voltage-gated ion channel mutations Ligand-gatedion channel (neurotransmitter receptor) mutations Acquired Auto-immune (anti- potassium channel antibodies) Changes in channel expression after seizures Epilepsy and Channelopathies
- 26. Epileptogenesis “Time Zero” Initial Insult EpileptogenicEvent Minutes/ hours Days Weeks Months Precipitatinginjury Spontaneous recurrent seizures Epilepsy Cascade of events? Biomarkers? Therapeutic Targets? Glu-Ca activation Ion-channel activation Post-transitional changes Immediate early genes Apoptosis Neuronal death Inflammation Glial response Vascular response Sprouting &Synaptogenesis Network reorganization Neurogenesis Angiogenesis Gliosis
- 27. Epileptogenesis “Time Zero” Initial Insult EpileptogenicEvent Minutes/ hours Days Weeks Months Precipitatinginjury Glu-Ca activation Ion-channel activation Post-transitional changes Immediate early genes
- 28.
- 29. Epileptogenesis “Time Zero” Initial Insult EpileptogenicEvent Minutes/ hours Days Weeks Months Precipitatinginjury Inflammation Glial response Vascular response Apoptosis Neuronal death
- 30. Epileptogenesis “Time Zero” Initial Insult EpileptogenicEvent Minutes/ hours Days Weeks Months Precipitatinginjury Sprouting &Synaptogenesis Network reorganization Neurogenesis Angiogenesis Gliosis
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- 32.
- 33. Loop structure ofhippocampus
- 34. Normal interneuronal inhibitory loop Epileptogenic Loop Loopstructure of hippocampus
- 35. Structural and molecularchanges associated with epileptogenesis 1. Selective neuronal loss. 2. Axonal &Dendritic Reorganisation including MFS. 3. Neurogenesis: dispersion of dentate granule cell layer and appearance of new ectopic cells. 4. Altered expression of neurotransmitter and their receptors. 5. Changes at glial architecture.
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- 44. Signaling pathways/Trancription factors /Epigenetics Gene expression Molecular Anatomical Circiut
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- 47. Signaling pathways/Trancription factors /Epigenetics Gene expression Molecular Anatomical Circiut AEG
- 48. AEG • Prevention canbe complete or partial. • Complete prevention aborts the development of epilepsy. • Partial prevention can delay the development of epilepsy or reduce its severity.
- 49.
- 50. AGENDA • Basic conceptsof epilepsy • Epileptogenesis • Classification of Epilepsy • Diagnosis of Epilepsy • Treatment options and strategies
- 51. Simple Complex 1. w/motor signs 2. w/ somato- sensory symptoms 3. w/ autonomic symptoms 4. w/ psychic symptoms 1. simple partial --> loss of consciousness 2. w/ loss of consciousness at onset Secondary generalized 1. simple partial --> generalized 2. complex partial --> generalized 3. simple partial --> complex partial --> generalized Partial seizures
- 52.
- 53. Operational classification ofseizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology, Volume: 58, Issue: 4, Pages: 522-530, First published: 08 March 2017, DOI: (10.1111/epi.13670) ILAE 2017 Classification of seizure type
- 54. Operational classification ofseizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology, Volume: 58, Issue: 4, Pages: 522-530, First published: 08 March 2017, DOI: (10.1111/epi.13670) ILAE 2017 Classification of seizure type
- 55. ILAE 2017 Classificationof seizure type
- 56. AGENDA • Basic conceptsof epilepsy • Epileptogenesis • Classification of Epilepsy • Diagnosis of Epilepsy • Treatment options and strategies.
- 57. • Not epileptic •Wrong seizure type (semiology) • Wrong epileptic syndrome • Wrong interpretation of EEG and imaging Tips and tricks in DIAGNOSIS of Epilepsy
- 58. Diagnosis of Epilepsy 58 Axis1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Axis 3: • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes
- 59. Diagnosis of Epilepsy 59 Axis1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Axis 3: • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes Axis 1: • Is it epileptic seizure or not? D.D. Of epilepsy
- 60. AXIS 1: D.D.OF EPILEPSY 60 Episodic impairment of consciousness 1. Impaired cerebral perfusion e.g. TIAs 2. Syncope. 3. Metabolic disturbances (e.g.,hypoglycemia). 4. Sudden increase in intracranial pressure. 5. Sleep disorders. 6. Movement disorders. 7. Psychologically – related phenomena.
- 61. PseudoSeizures Non-epileptic seizure Epilepticseizure Duration Prolonged (several minutes) Usually less than 2-3 minutes Clinical features • Fluctuating features • Usually during wakefulness • Preserved consciousness, avoidance behavior • Side to side head movements • Out of phase extremity movements • Forward pelvic thrusting • Emotional vocalization • Pupillary reflex retained • Stereotypic features • May occur in sleep • Altered consciousness • Head unilaterally turned • In phase extremity movements • Retropelvic thrusting • Monotonous vocalization • Pupillary reflex absent Incontinence Rare Present Tongue bite Occasional Common Postictal changes None Usually present Affect La Belle indifference Concerned
- 62. 62 Axis 1: • Isit epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Axis 3: • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes Axis 1: • Is it epileptic seizure or not? D.D. Of epilepsy Diagnosis of Epilepsy
- 63. 63 Axis 1: • Isit epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Axis 3: • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes Axis 1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Diagnosis of Epilepsy
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- 66.
- 67. Operational classification ofseizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology, Volume: 58, Issue: 4, Pages: 522-530, First published: 08 March 2017, DOI: (10.1111/epi.13670) ILAE 2017 Classification of seizure type
- 68. International Classification ofEpilepsy :CPS
- 69. Operational classification ofseizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology, Volume: 58, Issue: 4, Pages: 522-530, First published: 08 March 2017, DOI: (10.1111/epi.13670) ILAE 2017 Classification of seizure type
- 70. Gen. Absences CPS Aura- +/- Onset Abrupt Gradual or abrupt Duration <15 sec >30 sec Termination Abrupt Usually Gradual Postictal S & S - Most often + Frequency Many daily Weekly-monthly PPT by HV Usually Unlikely Absence Vs CPS
- 71. • Male child, 10 years old • Unreventful past medical history. • His mother noticed recurrent attacks of head and eye deviation to the right side associated with clonic movements involving the right upper limb that occur frequently and lasted for few minutes (according to her own words). Case Vignette
- 72. • Neurological examinationwas unremarkable. • The patient’s family could not afford the requested investigations due to financial issues. Case Vignette
- 73. Which AED wouldyou like to choose? • CBZ • VPA • LEV • OXC • TPM • OTHERS Case Vignette
- 74. Which AED wouldyou like to choose? • CBZ 200 mg CR bid • VPA • LEV • OXC • TPM • OTHERS Case Vignette
- 75. • In thefollow up visit, the patient’s mother reported no improvement as regard the seizure frequency. Case Vignette
- 76. What do youthink? • Increase dose of CBZ • Consider Adding another AED • Consider replacing CBZ with another AED. Case Vignette
- 77. What do youthink? • Increase dose of CBZ 400 CR mg BID • Consider Adding another AED • Consider replacing CBZ with another AED. Case Vignette
- 78. • Again, inthe follow up visit, the patient’s mother reported no improvement as regard the seizure frequency. Case Vignette
- 79. What do youthink? • Increase dose of CBZ • Consider adding another AED • Consider replacing CBZ with another AED. Case Vignette
- 80. What do youthink? • Increase dose of CBZ • Consider adding another AED LEV 250 BID • Consider replacing CBZ with another AED. Case Vignette
- 81. • In thefollow up visit, the patient’s mother reported partial reduction in the seizure frequency. Case Vignette
- 82. Operational classification ofseizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology, Volume: 58, Issue: 4, Pages: 522-530, First published: 08 March 2017, DOI: (10.1111/epi.13670) ILAE 2017 Classification of seizure type
- 83. Diagnosis of Epilepsy 83 Axis1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Axis 3: • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes Axis 1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures.
- 84. Diagnosis of Epilepsy 84 Axis1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Axis 3: • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes Axis 1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures.
- 85. AXIS 3: INVESTIGATIONS Labs 85 Shouldbe tailored according to the case; • Drug screen • Electrolytes • KFT • LFT • CSF examination • Lactic acid
- 86. AXIS 3: INVESTIGATIONS EEG 86 ConventionalElectroencephalography • Used in establishing the diagnosis and focality of an epileptic disorder • Normal EEG doesnot exclude presence of epilepsy thus the yield of EEG can be increased by Sleep deprivation (< 4 h sleep )
- 87. AXIS 3: INVESTIGATIONS EEG 87 MultipleElectroencephalography (EEG) exams EEG monitoring with video (video-EEG)
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- 91.
- 92. Diagnosis of Epilepsy 92 Axis1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Axis 3: • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes Axis 1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 3:
- 93. Diagnosis of Epilepsy 93 Axis1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Axis 3: • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes Axis 1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 3: Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes
- 94.
- 95. Neonatal period Benign familialneonatal seizures (BFNS) Early myoclonic encephalopathy (EME) Ohtahara syndrome Infancy West syndrome Myoclonic epilepsy in infancy (MEI) Benign infantile seizures Benign familial infantile seizures Dravet syndrome Myoclonic encephalopathy Childhood Febrile seizures plus (FS+) (can start in infancy) Early onset benign childhood occipital epilepsy (Panayiotopoulos type) Epilepsy with myoclonic atonic (previously astatic) seizures Benign epilepsy with centrotemporal spikes (BECTS) Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) Late onset childhood occipital epilepsy (Gastaut type) Epilepsy with myoclonic absences Lennox-Gastaut syndrome Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) Landau-Kleffner syndrome (LKS) Childhood absence epilepsy (CAE) AXIS 4: IDENTIFY EPILEPTIC SYNDROME EPILEPTIC SYNDROMES
- 96. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES 96 EPILEPTIC SYNDROME IS DEFINED BY 1. Type or types of seizure e.g. Absence ,GTC. 2. Age of seizure onset 3. Aetiology 4. Degree of neurologic and intellectual deficit 5. Clinical evolution of the epilepsy 6. EEG pattern 7. Neuroimaging abnormality
- 97.
- 98. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES 98 Benign epilepsy of childhood with centrotemporal spikes Common characteristic features includes : • Unilateral somatosensory involvement. • Speech arrest. • Preservation of consciousness in most cases. • Pooling of saliva &Tonic or tonic-clonic spread to face.
- 99. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES 99 • The typical interictal EEG shows centrotemporal spikes or SW, which are either unifocal or bifocal. • Carbamazepine is often the first medication to be tried, and seizures usually are well controlled. • Excellent prognosis. Benign epilepsy of childhood with centrotemporal spikes
- 100.
- 101. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES 10 1 Childhood epilepsy with occipital paroxysms: • Early onset type : • Young childern 5 ys • Ictal vomiting , deviation of the eye ,impairment of the consciousness sometimes progress into GTCs • Two thirds of seizures occur during sleep
- 102. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES 102 Panayiotopoulos syndrome • Previously called early-benign childhood seizures with occipital spikes • Childhood onset (peak 5 years). • Focal autonomic seizures or autonomic status epilepticus, frequently with emesis. • Interictal EEG with shifting or multifocal high amplitude spikes, often with occipital predominance.
- 103. Panayiotopoulos syndrome 103 Panayiotopoulos syndrome •Favorable outcome with remission in 1–2 years and normal development. • EEG spikes occur most commonly in the posterior areas of the brain including the occipital lobe • 30% of patients show only extraoccipital discharge or normal EEGs
- 104. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES
- 105. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES Childhood epilepsy with occipital paroxysms: • Late onset (Gastaut) type : • Older childern 9 ys • Formed visual hallucinations or amaurosis followed by hemiclonic convulsions with post- ictal migrain • EEG: occipital spikes • Excellent prognosis
- 106. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES 10 6 Childhood absence epilepsy • Seizure semiology: • Absence:Typical absence • High frequency hundreds / day • + Myoclonus • + GTCS • 3-12 years • EEG changes: 3-Hz spike and wave • Treatment : VPA, EXM • Favorable outcome( long term remission)
- 107.
- 108. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES West syndrome (infantile spasms): • Triad of : 1. Seizures 2. Psychomotor retardation or regression 3. Specific EEG changes : hypsarrythmia. • 1st year of life • Related to prenatal ,natal or postnatal insult
- 109. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES West syndrome (infantile spasms): • Seizures 1. Flexor spasms 2. Extensor spasms 3. Mixed flexor & extensor spasms • Resistant to treatment • Poor prognosis
- 110. AXIS 4: IDENTIFYEPILEPTIC SYNDROME EPILEPTIC SYNDROMES Lennox Gastaut syndrome • Mixed seizure disorder: • (Tonic, TC, Myoclonic, Atypical absence & drop attacks ) • Mental retradation EEG: Slow spike & wave Sharp & slow wave complex Slow abnormal background Treatment : commonly need Polytherapy Poor prognosis & cure rarely achieved
- 111. Diagnosis of Epilepsy Axis1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. Axis 3: • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes Axis 1: • Is it epileptic seizure or not? D.D. Of epilepsy Axis 2: • Identify type of seizure (seizure semiology) International classification of epileptic seizures. • Investigations aiming at confirmation of the diagnosis & searching for an aetiology Axis 3: Axis 4: • Identify epileptic syndrome International classification of epilepsy & epileptic syndromes
- 112. AGENDA • Basic conceptsof epilepsy • Epileptogenesis • Classification of Epilepsy • Diagnosis of Epilepsy • Treatment options and strategies
- 113. Treatment pitfalls • Whento start a drug? • Which drug and in what dose? • When to change the drug? • When (and how) to add a second drug (and which one)? • When to stop the drug(s)? • When to consider alternative therapies, including surgery?
- 114. 1840 1860 18801900 1920 1940 1960 1980 2000 0 5 10 15 20 Bromide Phenobarbital Phenytoin Primidone Ethosuximide Sodium Valproate Benzodiazepines Carbamazepine Zonisamide Felbamate Gabapentin Topiramate Fosphenytoin OxcarbazepineTiagabine Levetiracetam Rufinamide Lacosamide Pregabalin Calendar Year NumberofLicensedAntiepilepticDrugs Lamotrigine Vigabatrin Perampanel Retigabine Levetiracetam eslicarbazepine Antiepileptic Drugs (AEDs)
- 115. Mechanisms of actionof AEDs
- 116. Seizure type Epilepsy syndrome Efficacy Cost Pharmacokineticprofile Adverse effects American Epilepsy Society 2010 Considerations in Choosing AEDs
- 117. Seizure type Epilepsy syndrome Efficacy Cost Pharmacokineticprofile Adverse effects American Epilepsy Society 2010 Considerations in Choosing AEDs
- 118. AED Na+ channels Ca+ channels GABA Glutamate Others Clinicalefficacy (type of seizures/syndromes) CBZ + FS, GTCS CLB GABAA receptors Broad spectrum CZP GABAA receptors Broad spectrum ETS + Absence PB + GABAA receptors FS, GTCS, myoclonic PHT + FS, GTCS VPA GABAA receptors NMDA receptors Broad spectrum FBM + GABAA receptors NMDA receptors Atonic, tonic, atypical absence in LGS GPT + GABAB receptors FS Considerations in Choosing AEDs
- 119. AED Na+ channels Ca+ channels GABA Glutamate Others Clinicalefficacy (type of seizures/syndromes) CBZ + FS, GTCS CLB GABAA receptors Broad spectrum CZP GABAA receptors Broad spectrum ETS + Absence PB + GABAA receptors FS, GTCS, myoclonic PHT + FS, GTCS VPA GABAA receptors NMDA receptors Broad spectrum FBM + GABAA receptors NMDA receptors Atonic, tonic, atypical absence in LGS GPT + GABAB receptors FS Considerations in Choosing AEDs
- 120. AED Na+ channels Ca+ channels GABA Glutamate Others Clinicalefficacy (type of seizures/syndromes) GVG GABA transaminase FS, infantile spasms LEV SV2A FS, GTCS, myoclonic LTG + + FS, GTCS, absence, infantile spasms OXC + FS, GTCS PGB + FS TGB GABA transporters FS TPM + GABAA receptors Carbonic anhydrase FS, GTCS, myoclonic, infantile spasms ZNS + + Carbonic anhydrase FS ESL + FS Considerations in Choosing AEDs
- 121. AED Na+ channels Ca+ channels GABA Glutamate Others Clinicalefficacy (type of seizures/syndromes) LCS + FS PER AMPA receptors FS RTG KCNQ channels FS RUF + FS, atonic, tonic in LGS STM Carbonic anhydrase FS STP GABAA receptors Dravet syndrome Anna Rosati et al., 2015 Considerations in Choosing AEDs
- 122. RICHARD E. APPLETONand J. HELEN CROSS, Drug treatment of paediatric epilepsy, chapter 30 Considerations in Choosing AEDs
- 123. Broad-Spectrum Agents Valproate Felbamate Lamotrigine Topiramate Zonisamide Levetiracetam Rufinamide* Vigabatrin Narrow-Spectrum Agents Partialonset seizures Phenytoin Carbamazepine Oxcarbazepine Gabapentin Pregabalin Tiagabine Lacosamide Eslicarbazepine American Epilepsy Society 2010 Absence Ethosuximide Considerations in Choosing AEDs
- 124. Seizure type Epilepsy syndrome Efficacy Cost Pharmacokineticprofile Adverse effects American Epilepsy Society 2010 Considerations in Choosing AEDs
- 125. Seizure type Epilepsy syndrome Efficacy Cost Pharmacokineticprofile Adverse effects American Epilepsy Society 2010 Considerations in Choosing AEDs
- 126. RICHARD E. APPLETONand J. HELEN CROSS, Drug treatment of paediatric epilepsy, chapter 30 Considerations in Choosing AEDs
- 127. RICHARD E. APPLETONand J. HELEN CROSS, Drug treatment of paediatric epilepsy, chapter 30 Considerations in Choosing AEDs
- 128. RICHARD E. APPLETONand J. HELEN CROSS, Drug treatment of paediatric epilepsy, chapter 30 Considerations in Choosing AEDs
- 129. Seizure type Epilepsy syndrome Efficacy Cost Pharmacokinetics Adverseeffects American Epilepsy Society 2010 Considerations in Choosing AEDs
- 130. Seizure type Epilepsy syndrome Efficacy Cost Pharmacokinetics Adverseeffects American Epilepsy Society 2010 Considerations in Choosing AEDs
- 131. AED Dosage (oral)(mg/kg/day) AEDs interactions CBZ 10–20 PB, VPA, LTG, ESL, LCS, PER, STP, CZP CLB 0.5–1 (maximum 30 mg/day) FBM, GVG, PGB, STP CZP 3–6 CBZ, PB, PHT, VPA ETS 20–30 VPA PB 3–5 < 5 years; 2–3 > 5 years CBZ, PHT, VPA, ESL, LCS, PER, RUF, STP, CZP PHT 8–10 < 3 years; 4–7 > 3 years PB, VPA, GVG, OXC, TPM, ESL, LCS, PER, RUF, STP, CZP Anna Rosati et al., 2015 Considerations in Choosing AEDs
- 132. AED Dosage (oral)(mg/kg/day) AEDs interactions VPA 15–40 CBZ, ETS, PB, PHT, LTG, TPM, CZP FBM 15–45 CLB GPT 25–35 GVG 20–80; 100–150 for infantile spasms CLB, PHT, RUF LEV 20–40 LTG 5–15 (add-on enzyme inducers); 1– 3 (add-on VPA); 1–5 (add-on VPA + inducers) CBZ, VPA, OXC, RUF, RTG Considerations in Choosing AEDs
- 133. AED Dosage (oral)(mg/kg/day) AEDs interactions TGB 0.5–2 PGB TPM 4–6 PHT, VPA, ZNS, ESL ZNS 4–12 TPM ESL 800–1200 mg/day (adults) CBZ, PB, PHT, TPM LCS 200–400 mg/day (adults) CBZ, PB, PHT PER 8–12 mg/day (>12 years) CBZ, PHT, PB, OXC Anna Rosati et al., 2015 Considerations in Choosing AEDs
- 134. AED Dosage (oral)(mg/kg/day) AEDs interactions RUF 30–40 PB, PHT, GVG, LTG STM 5 CLB STP 50 CBZ, CLB, PB, PHT Anna Rosati et al., 2015 Considerations in Choosing AEDs
- 135. Seizure type Epilepsy syndrome Efficacy Cost Pharmacokinetics Adverseeffects American Epilepsy Society 2010 Considerations in Choosing AEDs
- 136. Seizure type Epilepsy syndrome Efficacy Cost Pharmacokinetics Adverseeffects American Epilepsy Society 2010 Considerations in Choosing AEDs
- 137. AED Common AEsSevere AEs CBZ Ataxia, diplopia, rash Aplastic anaemia, agranulocytosis, liver toxicity, SJS/TEN, pancreatitis, SLE CLB Sedation No CZP Sedation No ETS Gastric discomfort, hiccups, rash, blurred vision, headache Aplastic anaemia, agranulocytosis, SJS/TEN, liver toxicity, SLE PB Behavioural problems, drowsiness, rash, cognitive impairment Agranulocytosis, SJS/TEN, liver toxicity, SLE PHT Ataxia, diplopia, nystagmus, acne, gum hypertrophy, hirsutism, cognitive and sedative affects, peripheral neuropathy Megaloblastic anaemia, lymphoma, agranulocytosis, SJS/TEN, liver toxicity, SLE, encephalopathy, choreoathetosis Considerations in Choosing AEDs
- 138. AED Common AEsSevere AEs VPA Nausea, epigastric pain, tremor, alopecia, weight gain, hyperammonaemia SJS/TEN, liver toxicity, SLE, pancreatitis, encephalopathy FBM Insomnia, somnolence, behavioural problems, movement disorders, vomiting, anorexia, urolithiasis. Aplastic anaemia, agranulocytosis, SJS/TEN, liver toxicity, pancreatitis, SLE GPT Asthenia, somnolence, depression, behavioural problems, ataxia, diplopia, rash, urinary incontinence. SJS/TEN, liver toxicity, behavioural problems VGB Sedation, behavioural problems, hallucinations, blurred vision, nausea, anorexia, weight gain, MRI abnormalities. Liver toxicity, pancreatitis, psychosis, visual field defects, encephalopathy . LEV Asthenia, somnolence, behavioural problems, hallucinations, headache, vomiting, infections. Psychotic events, liver toxicity, pancreatitis . LTG Behavioural problems, ataxia, tremor, dizziness, diplopia, dyskinesia, tics, nausea, Aplastic anaemia, SJS/TEN, liver toxicity, pancreatitis. Lyell’s Considerations in Choosing AEDs
- 139. AED Common AEsSevere AEs OXC Asthenia, somnolence, behavioural problems, ataxia, dizziness, diplopia, headache, abdominal pain, nausea, vomiting, rash, infections, fever SJS/TEN, liver toxicity PGB Somnolence, behavioural problems, dizziness, weight gain, ataxia TGB Asthenia, somnolence, behavioural problems, hallucinations, dizziness SJS/TEN, non convulsive status epilepticus TPM Asthenia, somnolence, aphasia, dysarthria, depression, behavioural problems, hallucinations, ataxia, dizziness, paresthesia, headache, diarrhoea, nausea, anorexia, hypohidrosis, urolithiasis, infections, fever SJS/TEN, liver toxicity, pancreatitis ZNS Asthenia, somnolence, behavioural problems, headache, constipation, diarrhoea, abdominal pain, nausea, vomiting, anorexia, rash, urolithiasis, infections, fever No Considerations in Choosing AEDs
- 140. AED Common AEsSevere AEs LCS Insomnia, somnolence, depression, suicidal ideation, behavioural problems, blurred vision, tics, nausea, haematological abnormalities. No PER Dizziness, nausea, somnolence, fatigue, irritability, headachea No RTG Dizziness, somnolence, headache, fatigue, confusional state, dysarthria, ataxia, blurred vision, tremor, nausea, urinary tract infectionsa [95] Suicidal ideationa [95] RUF Ashenia, somnolence, dizziness, diplopia, headache, nausea, vomiting, anorexia, rash No STM Somnolence, vomiting, restlessness, anorexia No STP Insomnia, somnolence, aphasia, dysarthria, behavioural problems, ataxia, tremor, diplopia, headache, abdominal No Considerations in Choosing AEDs
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- 142. Typically dose-related: Dizziness ,Fatigue , Ataxia, Diplopia all AEDs Irritability levetiracetam Word-finding difficulty, scholastic achievement topiramate Weight loss/anorexia topiramate, zonisamide, felbamate Weight gain valproate (also associated with polycystic ovarian syndrome ) carbamazepine, gabapentin, pregabalin American Epilepsy Society 2010 Considerations in Choosing AEDs
- 143. Typically Idiosyncratic: Renal stones topiramate, zonisamide Anhydrosis, heat stroke topiramate Acute closed-angle glaucoma topiramate Hyponatremia carbamazepine, oxcarbazepine American Epilepsy Society 2010 Considerations in Choosing AEDs
- 144. Serious AE Typically Idiosyncratic: Aplasticanemia felbamate, zonisamide, valproate, carbamazepine Hepatic Failure valproate, felbamate, lamotrigine, phenobarbital Peripheral vision loss vigabatrin Rash phenytoin, lamotrigine, zonisamide, carbamazepine American Epilepsy Society 2010 Considerations in Choosing AEDs
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- 147. Ketogenic deit Mainexperience with children, especially with multiple seizure types. Likely anti-seizure effect of ketosis (beta hydroxybutyrate), but other mechanisms also may be responsible for beneficial effects. Low carbohydrate, adequate protein, high fat. 50% with a >50% seizure reduction, 30% with >90% reduction. Side effects include kidney stones, weight loss, acidosis, dyslipidemia.
- 148. FDA approval1997 Patients with intractable epilepsy < 12ys 35% of patients have a 50% reduction in seizure frequency 20% experience a 75% reduction after 18 months of therapy. Vagal Nerve stimulation
- 149. • Epilepsy syndromenot responsive to medical management – Unacceptable seizure control despite maximum tolerated doses of 2-3 appropriate drugs as monotherapy • Potentially curative – Resection of epileptogenic region (“focus”) avoiding significant new neurologic deficit • Palliative – Partial resection of epileptogenic region – Disconnection procedure to prevent seizure spread • Callosotomy • Multiple subpial transections American Epilepsy Society 2010 Epileptic surgery
- 150. Seizure freedomfor 2 years implies overall >60% chance of successful withdrawal in some epilepsy syndromes. Favorable factors Control achieved easily on one drug at low dose. No previous unsuccessful attempts at withdrawal. Normal neurologic exam and EEG. Primary generalized seizures except JME. “Benign” syndrome. American Epilepsy Society 2010 Discontinuing AED
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- 153. Adequate sleep Avoidance of alcohol, stimulants, etc. Avoidance of known precipitants Stress reduction — specific techniques American Epilepsy Society 2010 Non-Drug Treatment/Lifestyle Modifications
- 154. AGENDA • Basic conceptsof epilepsy • Epileptogenesis • Classification of Epilepsy • Diagnosis of Epilepsy • Treatment options and strategies
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