Epilepsy Syndromes

Epilepsy Syndromes

1. Epilepsy Syndromes

2. Epilepsy is a disease of the brain defined by any of the following conditions At least two unprovoked (or reflex) seizures occurring >24 h apart 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 Diagnosis of an epilepsy syndrome

3. Syndromes in Neonates A . Self-Limited Epilepsy Syndromes Self-Limited (Familial) Neonatal Epilepsy Benign Neonatal Seizures B . Developmental and Epileptic Encephalopathies (DEE) Early-Infantile Developmental and Epileptic Encephalopathy ( Ohtahara syndrome and Early Myoclonic Encephalopathy (EME ))

4. Self-Limited (Familial) Neonatal Epilepsy Benign Familial Neonatal Epilepsy Benign Neonatal Seizures Age of onset days 2 and 3 fifth-day fits Seizures Focal clonic or focal tonic seizures may alternate sides may evolve to bilateral tonic- clonic seizure unifocal clonic and rarely focal tonic EEG minor non-specific abnormalities such as mild discontinuity or slowing EEG background may be normal or nonspecific, an ictal pattern called theta pointu alternant Development at onset normal Neurological exam Imaging To exclude structural lesion Other studies – genetics, etc AD mutations of the KCNQ2 gene including hypoglycemia, sepsis, and meningitis, are excluded. treatment Short term of BZD, phenytoin Long Term outcome Seizures typically remit by 6 months of age, the majority ceasing by 6 weeks of age events tend to dissipate after 2 days.

5. Other self limited in neonate or at infantile Self-Limited (Familial) Neonatal-Infantile Epilepsy (1 day to 23 months) Focal seizures are mandatory for diagnosis usually remit within 1 year

6. Early-Infantile Developmental and Epileptic Encephalopathy Early-onset Epileptic Encephalopathies ( Ohtahara syndrome) early myoclonic encephalopathy Age of onset neonatal period (Birth to 3 months) Seizures Tonic and/or myoclonic seizures myoclonic and/or tonic seizures EEG persistent burst-suppression pattern during both the awake and sleep states burst-suppression pattern during the sleep Development at onset developmental impairment Neurological exam Imaging MRI is not required but for exclude structural causes Other studies – genetics, etc structural malformations > metabolic disorders metabolic disorders>structural malformations treatment etiology-specific treatment is available ( eg , hemispherectomy for hemimegalencephaly or pyridoxine for pyridoxine dependency) West syndrome with infantile spasms or Lennox- Gastaut syndrome Long Term outcome

7. Syndromes in Infancy A. Self-Limited Epilepsy Syndromes Benign Myoclonic Epilepsy in Infancy Genetic Epilepsy with Febrile Seizures Plus (GEFS+) spectrum: including Febrile Seizures Plus B . Developmental and Epileptic Encephalopathies (DEE) Epilepsy of Infancy with Migrating Focal Seizures (EIMFS ) Infantile Spasms Syndrome Dravet Syndrome Etiology-Specific Syndromes

8. Benign Myoclonic Epilepsy in Infancy Age of onset 4 months and 3 years of age Seizures myoclonic seizures that triggered by sensory stimuli, whether tactile, auditory, or photic may be very subtle, especially at onset, with brief head nods or eye rolling EEG 3 Hz to 4 Hz generalized spike- or polyspike Development at onset Neurological exam Imaging Other studies – genetics, etc treatment Long Term outcome Generalized tonic- clonic seizures may be seen later in childhood

9. Genetic Epilepsy with Febrile Seizures Plus (GEFS+) spectrum: including Febrile Seizures Plus Age of onset infancy or childhood (6 month-6 years) Seizures simple febrile seizures to mixed febrile and afebrile seizures that may be prolonged, focal, or occur in clusters generalized and focal seizures EEG Development at onset Neurological exam Imaging Other studies – genetics, etc SCN1A gene treatment sodium channel blockers such as may be deleterious otherwise pharmacoresponsive epilepsy that typically remits by adolescenc Long Term outcome

10. Epilepsy of Infancy With Migrating Focal Seizures Age of onset before 12 months Seizures focal seizures with multiple topographic origins that migrate within and between cerebral hemispheres have a “ ping-pong ” or migratory quality EEG Ictal recording shows a migrating pattern Development at onset Developmental plateauing or regression with frequent seizures Neurological exam Imaging diagnosis to exclude a causal structural etiology Other studies – genetics, etc SCN1A or KCNT1 treatment AEDs, the ketogenic diet, and vagal nerve stimulation Long Term outcome Neurodevelopmental delay (rare and poor prognosis syndrome)

11. West Syndrome Epilepsy of Infantile Spasms Syndrome Age of onset 1-24 months Seizures Clusters of flexor, extensor or mixed epileptic spasms EEG hypsarrhythmia , multifocal or focal epileptiform discharges Development at onset Psychomotor retardation Neurological exam Imaging MRI is not required for diagnosis but is strongly recommended to exclude structural causes Other studies – genetics, etc Some genetic disorders have a strong association with infantile spasms ( eg , tuberous sclerosis complex and Down syndrome) treatment adrenocorticotropic hormone (ACTH), prednisolone, or the g- aminobutyric (GABA)-transaminase inhibitor vigabatrin Long Term outcome A high risk exists that patients will develop cognitive impairment, autism spectrum disorder, and chronic epilepsy, including Lennox- Gastaut syndrome

12. Severe Myoclonic Epilepsy of Infancy ( Dravet Syndrome) Age of onset 1-20 months Seizures hemiclonic seizures febrile seizures and go on to have recurrent febrile and afebrile myoclonic, focal, and generalized (atypical absence and convulsive) seizures The hemiclonic seizures aspect alternates sides EEG Development at onset cognitive decline and motor deficits Neurological exam Imaging MRI is not required for diagnosis but is strongly recommended to exclude structural causes Other studies – genetics, etc sodium channel gene SCN1A treatment valproate, clobazamas well as the ketogenic diet Long Term outcome Drug resistant epilepsy Intellectual disability status epilepticus as well as sudden unexpected death in epilepsy (SUDEP)

13. Etiology-Specific Syndromes KCNQ2-DEE Early-onset Vitamin-dependent CDKL5-DEE PCDH19 Clustering Epilepsy Glucose Transporter 1 Deficiency Syndrome Sturge -Weber syndrome Gelastic Seizures with Hypothalamic Hamartoma ( gelastic or dacrystic ) Focal clonic or focal tonic Epileptic encephalopathy Pharmacoresistant

14. Epilepsy Syndromes with Onset in Childhood ( 1) Self-Limited Focal Epilepsies of Childhood (2) Idiopathic Generalized Epilepsy Syndromes ( 2) Genetic Generalized Epilepsies ( 3) Developmental and/or Epileptic Encephalopathies of Childhood.

15. Self-Limited Focal Epilepsies of Childhood Self-Limited Epilepsy with Centrotemporal Spikes ( SeLECTS ) ( rolandic epilepsy) Self-Limited Epilepsy with Autonomic Seizures ( SeLEAS ) ( Panayiotopoulos syndrome) Childhood Occipital Visual Epilepsy (COVE ) ( Gastaut type) Photosensitive Occipital Lobe Epilepsy (POLE )

16. Self-Limited Epilepsy with Centrotemporal Spikes ( SeLECTS ) ( rolandic epilepsy) Age of onset 3 to 11 years Seizures Focal seizures wakefulness or sleep and/or nocturnal: paresthesia on one side of the tongue or mouth, followed by dysarthria or gagging-type noises, jerking of the ipsilateral face, and excessive drooling. focal to bilateral tonic clonic seizures in sleep only EEG High amplitude, centrotemporal biphasic spike-wave discharge Development at onset Neurological exam Imaging Other studies – genetics, etc treatment pharmacoresponsive epilepsy ( carbamazepine, oxcarbazepine , levetiracetam , lamotrigine , and valproate) Remission by mid to late adolescence Long Term outcome

17. Self-Limited Epilepsy with Autonomic Seizures ( SeLEAS ) (Panayiotopoulos syndrome) Age of onset between 3 and 6 years of age Seizures Focal autonomic seizures, with or without impaired awareness during sleep. Autonomic symptoms often involve prominent retching and vomiting, but may also include malaise, pallor, flushing, abdominal pain, pupillary or cardiorespiratory changes EEG High amplitude, focal or multifocal discharges which increase in drowsiness and sleep with the occipital regions involved in about half of recordings Development at onset Neurological exam Imaging Other studies – genetics, etc treatment Remission by early to mid adolescence No developmental regression Long Term outcome

18. Childhood Occipital Visual Epilepsy (COVE) ( Gastaut type) Age of onset 6 and 11 years Seizures Focal sensory visual seizures with elementary visual phenomena (multicolored circles), with or without impaired awareness, and with or without motor signs (deviation of the eyes or turning of the head) with postictal migrain . EEG Occipital spikes or spikes-and-wave discharges (awake or sleep). fixation off phenomenon: precipitated by eye closure and attenuated by eye opening Development at onset Neurological exam Imaging Other studies – genetics, etc treatment Long Term outcome

19. Photosensitive Occipital Lobe Epilepsy (POLE) Age of onset 4 and 17 Seizures Focal sensory visual seizures, which may evolve to bilateral tonic- clonic seizures. Seizures are triggered by photic stimuli, such as flickering sunlight EEG normal. Interictal occipital spike or spike Development at onset Neurological exam Imaging Other studies – genetics, etc treatment Long Term outcome variable

20. Idiopathic Generalized Epilepsy Syndromes Childhood Absence Epilepsy

21. Childhood Absence Epilepsy Age of onset 4-10 years girl more Seizures typical absence seizure, meaning abrupt impairment of consciousness, often with associated behavioral arrest, staring, eye fluttering, or automatisms At least daily to multiple per day but may be under-recognized by family Typical duration 3-20 seconds EEG generalized 3 Hz to 4 Hz spike-and-wave IPS triggers generalized spike-wave in 15% hyperventilation Development at onset Typically normal, but may have learning difficulties or ADHD Neurological exam NAD Imaging NAD Other studies – genetics, etc treatment ethosuximide , valproic acid, epilepsy is associated with seizure freedom and long-term remission in up to 75% of patients Long Term outcome

22. The Genetic Generalized Epilepsy Syndromes of Childhood Epilepsy with Myoclonic Absence ( Tassinari Syndrome) Epilepsy with Eyelid Myoclonia ( Jeavons Syndrome)

23. Epilepsy with Myoclonic Absence ( Tassinari Syndrome) Age of onset 1 to 12 years, and males predominate Seizures prominent rhythmic myoclonic or clonic activity during absence seizures EEG generalized 3 Hz spike-and-wave Development at onset Neurological exam intellectual disability may preset Imaging May needed Other studies – genetics polygenic treatment Remission in approximately 40% of patients.. Prognosis is variable Long Term outcome

24. Epilepsy with Eyelid Myoclonia ( Jeavons Syndrome) Age of onset 2 to 14 years, female predominate2:1 Seizures triad of frequent eyelid myoclonia , with or without absences, induced by eye closure and photic stimulation. Eyelid myoclonia is often most prominent on awakening Additional generalized tonic- clonic EEG EEG is similar to the generalized 3 to 6 Hz polyspike and wave complex Development at onset Neurological exam intellectual disability may preset Imaging May needed Other studies – genetics, etc Polygenic or monogenic treatment Remission in not rule .Prognosis is variable Long Term outcome

25. Developmental and/or Epileptic Encephalopathies of Childhood. Myoclonic-Atonic Epilepsy( Doose syndrome ). Lennox- Gastaut syndrome Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep. Febrile Infection-Related Epilepsy Syndrome (FIRES) Hemiconvulsion Hemiplegia-Epilepsy (HHE) syndrome

26. Myoclonic-Atonic Epilepsy ( Doose syndrome) Age of onset 2-6 years. Boys are more commonly affected Seizures Myoclonic followed by atonic seizures other seizure types occur, including absence, tonic- clonic , and tonic as well as myoclonic or nonconvulsive status epilepticus EEG Generalized 3-6 Hz spikewave or polyspike - andslow -wave discharges Development at onset Neurological exam intellectual disability may preset Imaging May needed Other studies – genetics, etc Polygenic or monogenic as SCN1A treatment Remission in not rule Prognosis is variable AED, ketogenic diet Vagus nerve stimulation corpus callosotomy unclear role Long Term outcome

27. Lennox- Gastaut syndrome Age of onset < 18 years Seizures Tonic seizures In addition Atypical absences • Atonic • Myoclonic • Focal impaired awareness • Generalized tonic clonic • Nonconvulsive status epilepticus • Epileptic spasms EEG slow spike-wave <2.5 Hz Generalized paroxysmal fast activity in sleep Development at onset Usually mentally retarded Neurological exam Imaging Other studies – genetics, etc Usually structural lesions, ( eg , focal cortical dysplasia, subcortical band heterotopia, perisylvian polymicrogyria ) as well as phakomatoses ( eg , tuberous sclerosis complex, hypomelanosis of Ito), meningitis or encephalitis, hypoxic-ischemic encephalopathy, and genetic epilepsies treatment Drug resistant epilepsy Long Term outcome Poor

28. Acquired Epileptic Aphasia (Landau- Kleffner Syndrome)

29. Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep. (D/EE-SWAS) Age of onset 2 and 12 years Seizures electroclinical syndrome mixed generalized seizures, cognitive deterioration No seizure specific according to etiology. EEG Continuous, slow (<2 HZ spike-wave in >50% of non-REM sleep) Development at onset Cognitive, behavioral or motor regression or plateauing temporally related to SWAS on EEG Neurological exam Imaging Other studies – genetics, etc malformations such as bilateral perisylvian polymicrogyria are associated with this syndrome treatment valproate, levetiracetam , benzodiazepines, corticosteroids, or other antiseizure medicines. Epilepsy surgery may be indicated if the patient has a resectable lesion. Long Term outcome Remission of SWAS pattern on EEG by mid adolescence, although EEG often remains abnormal

30. Febrile Infection-Related Epilepsy Syndrome (FIRES) Age of onset a rare syndrome, which is likely under-recognized, Seizures 2 week of febrile illness ----focal multifocal evolve to bilateral tonic clonic seizure Within tow week progress to super refractory seizure EEG Slowing of the background with multifocal discharges Development at onset Neurological exam Acute encephalopathy with onset of frequent seizures Imaging Approximately one third may show bilateral T2 hyperintense affect temboral lobe, basal ganglia and thalmi Other studies – genetics, etc treatment Long Term outcome Poor mortality is approximately 10%

31. Hemiconvulsion Hemiplegia-Epilepsy (HHE) syndrome Age of onset less than 4 years of age Seizures Acute stage: Episode of febrile,---- hemiclonic status epilepticus -----permanent hemiparesis Chronic stage: After a variable time<3 years unilateral focal motor or focal to bilateral tonic clonic seizures appear EEG Acute: Slowing of background activity over the affected chronic : hemisphere Focal or multifocal epileptiform discharges over the affected hemisphere in the chronic phase Development at onset Neurological exam Imaging Acute: hyperintensity subcortical region of the affected hemisphere, often with severe edema. chronic stage: there is atrophy of the affected hemisphere Other studies – genetics, etc treatment Drug-resistant epilepsy Permanent focal motor deficit Long Term outcome

32. ILAE Classification and Definition of Epilepsy Syndromes with Onset at a Variable Age generalized epilepsy syndromes, with presumed polygenic etiologies focal epilepsy syndromes with genetic, structural or genetic-structural etiologies generalized and focal epilepsy syndrome with polygenic etiology a specific group of developmental and/or epileptic encephalopathies etiology-specific epilepsy

33. generalized epilepsy syndromes, with presumed polygenic etiologies juvenile absence epilepsy juvenile myoclonic epilepsy epilepsy with generalized tonic- clonic seizures alone

34. generalized epilepsy syndromes, with presumed polygenic etiologies juvenile absence epilepsy juvenile myoclonic epilepsy epilepsy with generalized tonic- clonic seizures alone Adolescent or early adulthood At 15 12-18 5-40 absence myoclonic seizure generalized tonic- clonic seizures 2hours after awakening, trigger by sleep deprivation 3-5.5 Hz generalized spike-wave Normal development Pharmacoresponsive but complete remission may not occur ethosuximide , valproate or lamotrigine Valproate, Levetiracetam or lamotrigine

35. focal epilepsy syndromes with genetic, structural or genetic-structural etiologies sleep related hypermotor epilepsy familial focal epilepsy with variable foci epilepsy with auditory features

36. focal epilepsy syndromes with genetic, structural or genetic-structural etiologies sleep related hypermotor epilepsy familial focal epilepsy with variable foci epilepsy with auditory features At adolescent but may in childhood or adulthood Night focal seizure (hyperkinetic-tonic or dystonic) Day time focal seizure (motor, autonomic or cognitive) Focal auditory If unilateral have lateralization value EEG non specific EEG non specific show intermittent midtemporal slowing MRI may Normal or focal cortical dysplasia Normal development KCNT1 mutations of the mechanistic target of rapamycin ( mTOR ) pathway inhibitor gene LGI AD mutation in half of cases Pharmacoresponsive but may need polytheraby also may be refractory

37. generalized and focal epilepsy syndrome with polygenic etiology reading-induced seizures

38. Reflex Epilepsies Now Epilepsy with reading-induced seizures Age of onset late teens, Male more than female 2:1 Seizures reflex myoclonic seizures affecting orofacial muscles triggered by reading if reading continues these may worsen and a generalized tonicclonic seizure may occur EEG NAD Development at onset Neurological exam Imaging MRI is required for diagnosis to exclude a structural cause. Other studies – genetics, etc treatment good response to specific ASM With good remission Long Term outcome

39. a specific group of developmental and/or epileptic encephalopathies

40. Progressive Myoclonus Epilepsies Age of onset Up to 50 Yrs Seizures myoclonus (cortical and subcortical) Generalized tonic- clonic seizures can also occur. EEG generalized spike- or polyspike -and-wave Development at onset Progressive cognitive decline, progressive cerebellar signs Neurological exam Imaging Other studies – genetics, etc treatment Poor tend to pharmacoresistant Long Term outcome

41. Unverricht-Lundborg disease AR point mutations in the cystatin B gene onset is between 6 and 16 years a Lafora body disease AR NHLRC1 encodes for laforin vision loss may present intracellular neuronal inclusions that are positive using histologic periodic acid-Schiff staining. MERRF mitochondrial disorder Second decade Vision and hearing loss may affected Muscle biopsy reveals so-called ragged red fibers on Gomori trichrome staining Neuronal ceroid lipofuscinoses lysosomal storage diseases AR range from infantile to adolescent and adult onset vision loss, pyramidal and extrapyramidal dysfunction, and seizures sialdosis red spots (cherry-red macules) 

42. Etiology-specific epilepsy Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis Rasmussen encephalitis

43. Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis Age of onset early childhood but is frequently in adolescence or early adulthood Seizures Focal aware or impaired awareness seizures with initial semiology referable to medial temporal lobe EEG 5 Hz to 9 Hz theta to alpha frequency range, maximally present at the anterior temporal region Development at onset Neurological exam Imaging Hippocampal sclerosis (unilateral or bilateral) on MRI Other studies – genetics Treatment Long Term outcome unlikely to respond to antiseizure medicines

44. autonomic or abdominal auras behavioral arrest Automatisms accompany these events, such as lip smacking, swallowing, chewing, or picking dystonic posturing of the upper extremity contralateral to the temporal lobe focus “ ictal speech,” meaning the patient has the ability to speak during the seizure, lateralizes the seizure focus to the nondominant (usually right) Postictal nose wiping is done by the hand ipsilateral to the focus

45. Rasmussen encephalitis Age of onset children, adolescents and young adults Seizures Focal/hemispheric seizures which often increase in frequency over weeks to month epilepsia partialis continua EEG Hemispheric slowing and interictal discharges Development at onset Neurological exam immune-mediated epilepsy progressive neurological impairment (hemiparesis, homonymous hemianopia, cognitive impairment) Imaging Progressive hemiatrophy Other studies – genetics, etc treatment Drug resistant epilepsy Progressive neurological Deficits hemispherectomy are the only known Long Term outcome