Syndromic Diagnosis and Interictal Correlation of Epilepsies

Dr.Ashraf.V.V

Consultant Neurologist MIMS Hospital, Calicut

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

2

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 3

Advantages of a syndromic diagnosis

Provide information about

– Age of onset – Etiology – Seizure type – Precipitating factors – Chronicity – Prognosis – Choice of treatment 4

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 5

Neonatal Epileptic syndromes

• Early Myoclonic encephalopathy • Ohtahara syndrome • Benign familial neonatal seizures 6

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 7

8

3 months later

9

Early Infantile Epileptic Encephalopathy

(

Ohtahara 1976)

• Onset in the first weeks of life • Characteristic repetitive ‘

tonic spasms’

generalized - focal or • 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 10

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

11

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 12

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 13

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 14

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 15

16

17

Inter-ictal Hypsarrthymmia (50-60%)

: Chaotic background with high amplitude delta,asynchronous multifocal spikes, polyspikes and electrodecremental activity Awake 18

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

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

Ictal

- Generalised sharpwaves/slow waves with attenuation 21

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 22

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

• EEGs normal ; later generalized epileptic photosensitivity

• Consider this syndrome when febrile / illness provoked seizures start in infancy and EEG is persistently NORMAL 24

EM-AS

GEFS +

SCN1A mutations DRAVETs SIGEI 25

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 26

Malignant migrating partial epilepsy of infancy

Migrating seizures of infantile

27

Migrating seizures of infantile

28

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 29

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 30

Ictal Semiology

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

31

32

Panayiotopoulos Syndrome

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

33

34

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 35

36

• •

Epileptic Encephalopathy of Late Childhood

A spectrum of diseases 1. Landau- Kleffner syndrome 2. CSWS Syndrome CSWS Gradual cognitive/behavior deterioration Acquired language impairment LKS • Seizures • Dramatic activation of epileptiform abnormalities in slow wave sleep

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 38

LKS Vs Epilepsy with CSWS

»

LKS Epilepsy with CSWS

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

40

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

41

42

Lennox Gastaut Syndrome

•

Polymorphic seizures

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

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 44

45

46

EVOLUTION OF SYNDROMES

OTAHARA’S (neonate) WEST (infant) LENNOX GASTAUT (toddler) 47

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

48

Epileptic spasms a few months later HYPSARRYTHMIA MODIFIED BY SLEEP 49

2.5 y; MR, Tonic seizures in sleep; Drop attacks with injuries; Episodes of atypical absence status & regression

SLOW SPIKE WAVE-LGS

50

Epilepsy with Myoclonic-Astatic Seizures( Doose Syndrome)

• Normal development prior to the onset • Onset peaks at 2-4 years • Two-thirds of children have febrile and afebrile GTCS to begin with • Myoclonic astatic seizures (post myoclonic atonia) • Normal background EEG with 2-3 Hz GSWD 51

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE)

• Hypermotor seizures • Consciousness is usually preserved • Postictal state is entirely normal • Common in hypnagogic state or shortly before awakening • Interictal EEG is usually normal • Video-polysomnographic EEG – frontal ictal rhythms in 30% of cases 52

Childhood Absence Epilepsy

• • • 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 53

OIRDA 54

3 Hz GSWD, Higher voltage in the anterior region, No marked variation in intradischarge frequency, no fragmentation in the ictal discharge 55

Epilepsy with Myoclonic Absences 56

Syndromes in Adolescence-Adults

• Juvenile Myoclonic epilepsy • Juvenile absence epilepsy • Epilepsy with GTCS alone • Autosomal dominant partial epilepsy with auditory features (ADPEAF) • Progressive myoclonic epilepsies 57

Juvenile Myoclonic Epilepsy

• Most common among IGEs: 4-6% • Genetically determined • 40-50 %: family history of epilepsy • Myoclonic seizures (MSs): 100% • Generalized tonic-clonic seizures: 90% • Absence seizures: 35% • EEG-3-6 Hz spike/polyspike-slow waves with intradischarge fragmentation and unstable frequency • One third of patients have photoparoxysmal responses 58

59

Juvenile Absence Epilepsy

• Usual age of onset 10-14 years • Typical Absences- impairement of consciousness • GTCS – In nearly 80% of patients • Myoclonic jerks -random • Absences>GTCS>Myoclonic jerks • Ictal EEG shows 3-4 Hz GSWD 60

Progressive Myoclonic Epilepsies

• Symptomatic generalized epilepsies • • Myoclonic seizures • • Progressive neurological abnormalities • MERRF: early childhood or as late as 65 yr of age • • Unverricht-Lundborg disease: 6-15 yr (mean 11 yr) Lafora’s disease: 10-18 yr • Neuronal ceroid lipofuscinosis • Sialidosis 61

62

63

Reflex Epilepsies

• Reading Epilepsy • Idiopathic photosensitive occipital epilepsy • Startle Epilepsy • Eyelid Myoclonia with absences (Jeavons Syndrome) 64

Reading Epilepsy

• Stimulus: reading, talking (fast or argumentative), writing.

• Manifests as myoclonic jerks of the jaw muscles • Other types of seizures is exceptional • Symptomatic form can have focal seizures manifesting with alexia and dysphasia • Interictal EEG is usually normal 65

Idiopathic photosensitive occipital epilepsy

• Visual hallucinations • Blurring of vision and blindness • Seizures induced by photic stimuli • Commonly induced by video games • Photic stimulation elicits PPR spikes 66

67

Jeavons Syndrome

• Age group : 6-8years • F>M • Eyelid myoclonia with and without absences • Eye closure induced seizures or EEG paroxysms • Photosensitivity 68

69

Diagnosis of epileptic syndromes problems • Exact diagnosis may not be possible on first contact • Needs periodic follow up • Evolution of syndrome eg: west syndrome  LGS • Overlapping features 70

THANK YOU

71