Syndromic Diagnosis and Interictal Correlation of Epilepsies

1. Syndromic Diagnosis and Interictal Correlation of Epilepsies Dr.Ashraf.V.V Consultant Neurologist MIMS Hospital, Calicut

2. Electro-clinical Syndrome • Group of clinical entities that are reliably identified by a cluster of electro-clinical and developmental characteristics • Largely genetic in origin • Tend to have a strong relationship to developmental aspects of brain ILAE Commission 2009

3. Concept of Epileptic Syndromes • Factors taken into consideration include • Seizure type(s) • Age of Onset • Precipitating factors • Severity, Chronicity • Diurnal/circadian cycling • Etiology: genetics, structural pathology • Associated neurological problems • Interictal EEG

4. Advantages of a syndromic diagnosis Provide information about • Age of onset • Etiology • Seizure type • Precipitating factors • Chronicity • Prognosis • Choice of treatment

5. Epileptic Encephalopathy • Electro-clinical syndrome associated with a very high probability of encephalopathic features that present or worsen after the onset of epilepsy • Pharmaco-resistant

6. Neonatal Epileptic syndromes • Early Myoclonic encephalopathy • Ohtahara syndrome • Benign familial neonatal seizures

7. Early Myoclonic Encephalopathy(Aicardi et al 1978) • Onset: first weeks of life • Erratic, focal, rarely generalized myoclonic and clonic seizures • High incidence of consanguinity • Sometimes IEMs: (NKHG) • EEG: Burst- Suppression Pattern, persists for months; awake & sleep • Intractable to therapy - seizure pattern may change over time • Severe disability; early death

9. 3 months later

10. Early Infantile Epileptic Encephalopathy (Ohtahara 1976) • Onset in the first weeks of life • Characteristic repetitive ‘tonic spasms’ - focal or generalized • Commonly associated with structural brain abnormalities • EEG burst suppression pattern, > in sleep, evolves to hypsarrythmia • Intractable to AEDs • Neurological outcome is very poor, early death • Evolves to WS, LGS

11. Fp1-F3 F3 –C3 C3 – P3 P3 – O1 Fp2 F4 F4 – C4 C4 – P4 P4 – O2 Fp1 –F7 F7 – T3 T3 – T5 T5 – O1 Fp2 F8 F8 – T4 T4 – T6 T6 – O2 EKG

12. Benign familial neonatal Seizures • Second or third day of life • Repetitive isolated seizures • Autosomal dominant • 10-15% develop epilepsy later • No psychomotor deficit • EEG: Non specific, focal abnormalities

13. Electro-clinical syndromes of Infancy • West syndrome • Febrile seizures plus • Dravet syndrome • Migrating partial seizures of infancy • Myoclonic epilepsy in infancy • Myoclonic encephalopathy in nonprogressive disorders • Benign familial infantile seizures

14. WEST SYNDROME : INFANTILE (EPILEPTIC) SPASMS • Myoclonic < Spasms< Tonic • Flexor , Extensor, Flexor-extensor • Subtle spasm • Asymmetrical spasm in symptomatic • Onset 3-12 m (4 months); till 2 yrs • Occipital lesions----early onset Frontal lesions -----later onset

15. West Syndrome • Symptomatic , Cryptogenic, Idiopathic • Symptomatic- cortical malformations, HIE, tuberous sclerosis,infections, genetic and chromosomal abnormalities etc • Focal lesions ++ • Autistic regression / visual agnosia • Evolution LGS / partial seizures

18. Inter-ictal Hypsarrthymmia (50-60%): Chaotic background with high amplitude delta,asynchronous multifocal spikes, polyspikes and electrodecremental activity Awake

19. Hypsarrhythmia with focal slowing (Left temporo-occipital FCD )

20. Spasms & hypsarrhythmia resolve by 2y Evolve to focal seizures (R occipital lesion)

21. Ictal- Generalised sharpwaves/slow waves with attenuation

22. WHEN FEBRILE SEIZURES ARE NOT FEBRILE SEIZURES • GEFS + (Gen. Epilepsy febrile seizures plus) • Common under-recognised disorder • Autosomal dominant with high penetrance • Typical FS, FS + lasting longer, Afebrile GTCs most common • Occasionally absence, myoclonic, atonic • Focal seizures of frontal or temporal lobe in origin • Dravet’s syndrome overlap • Remits in adolescence 80% • Sodium channelopathy

23. Dravet’s syndrome (SMEI) • 1st year febrile / afebrile unilateral / GTCs; status epilepticus • Later myoclonus, atypical absence, complex focal • Resistant to AEDs • Cognitive regression, ataxia 2nd year • FH + 25-30% • Severe idiopathic generalised epilepsy of infancy (SIGEI) with GTCs: No myoclonus

24. EEGs normal ; later generalized epileptic photosensitivity • Consider this syndrome when febrile / illness provoked seizures start in infancy and EEG is persistently NORMAL

25. EM-AS GEFS + SCN1A mutations DRAVETs SIGEI

26. Malignant migrating partial epilepsy of Infancy • Epileptic encephalopathy • Mean age 3 months • Continuous multifocal seizures arising independently from multiple regions • Psychomotor deterioration • Seizure control is exceptional

27. Malignant migrating partial epilepsy of infancy Migrating seizures of infantile

28. Migrating seizures of infantile

29. Childhood epilepsy syndromes • Benign epilepsy with centrotemporal spikes • Early onset Benign childhood occipital epilepsy (Panayiotopoulos Syndrome) • Late onset childhood occipital epilepsy (Gastaut type) • Epileptic encephalopathy with CSWS • Landau-Kleffner syndrome • Lennox-Gastaut syndrome • Autosomal dominant nocturnal frontal lobe epilepsy • Childhood Absence epilepsy • Epilepsy with myoclonic absence

30. BECTS[Benign Rolandic Epilepsy] • Most common partial epilepsy in childhood • Onset 2-14 years; ¾ 7-10 yrs • Seizure frequency- • 10-20% have a single seizure • 20% have frequent seizures • < 2% have seizures into adulthood • “No other” neurological issues

31. Ictal Semiology Focalfacial sensorimotor 70% nocturnal 60% retained awareness Lasts 1-2 min Sec. Generalized- 30-50% Oro-pharyngo-laryngeal Hyper salivation Speech arrest Clonic upperlimb

33. Panayiotopoulos Syndrome Tonic eye deviation 70% nocturnal Peak- 4 to 5 years Lasts longer; 44% > 30 min EEG focus-commonly occipital, variability ++ N, R, Vomiting Pallor + other autonomic Ictal syncope

35. Idiopathic childhood occipital epilepsy of Gastaut • Mean age : 8 years • Elementary visual hallucinations • Ictal blindness • Deviation of eyes • Severe headache • EEG shows occipital paroxysms, often demonstrating fixation-off sensitivity

37. Epileptic Encephalopathy of Late Childhood LKS CSWS A spectrum of diseases Landau- Kleffner syndrome CSWS Syndrome Gradual cognitive/behavior deterioration Acquired language impairment Seizures Dramatic activation of epileptiform abnormalities in slow wave sleep

38. Landau Kleffner Syndrome • Our son was normal in every way until the age of 2 years. At first he seemed to be losing his hearing but not for environmental sounds. We thought that he was going deaf, but the hearing test was normal… When he was 3 years old he didn’t say anything for over a month. He improved for a few months and then he had a minor seizure • From the internet description by a mother

39. LKS CSWS 80% Spikes Temporal Seizures 75% Symptomatic rare Verbal auditory agnosia Behavioural deficit common 50% reach near normal life Epilepsy with CSWS CSWS 100% Frontal spikes Seizures -100% One third symptomatic Expressive aphasia Nearly all One-quarter reach normal LKS Vs Epilepsy with CSWS

41. Fp1-F3 F3 –C3 C3 – P3 P3 – O1 Fp2 F4 F4 – C4 C4 – P4 P4 – O2 Fp1 –F7 F7 – T3 T3 – T5 T5 – O1 Fp2 F8 F8 – T4 T4 – T6 T6 – O2 EKG

43. Lennox Gastaut Syndrome • Polymorphic seizures Tonic Seizures - Commonest Atypical absences – 2/3rd of patients Atonic seizures (Drop attacks) Myoclonic jerks • Cognitive and behavioural abnormalities • EEGSlow spike and wave, Paroxysms of fast activity

44. Lennox-Gastaut Syndrome • Peak age 3-5 years • Symptomatic form most common • One third idiopathic • No genetic predisposition • Half of the West syndrome and others progress to LGS • Poor prognosis

47. EVOLUTION OF SYNDROMES OTAHARA’S (neonate) WEST (infant) LENNOX GASTAUT (toddler)

48. D 15 infant refractory tonic / partial seizures; BH N MRI N / Metabolic N EE with suppression – burst (OTOHARA’s )

49. Epileptic spasms a few months later HYPSARRYTHMIA MODIFIED BY SLEEP

50. 2.5 y; MR, Tonic seizures in sleep; Drop attacks with injuries; Episodes of atypical absence status & regression SLOW SPIKE WAVE-LGS