Syndromic Diagnosis and Interictal Correlation of Epilepsies

Dr.Ashraf.V.V

Consultant Neurologist

MIMS Hospital, Calicut

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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

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• 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

Concept of Epileptic Syndromes

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Advantages of a syndromic diagnosis

Provide information about– Age of onset– Etiology– Seizure type– Precipitating factors– Chronicity– Prognosis– Choice of treatment

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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

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Neonatal Epileptic syndromes

• Early Myoclonic encephalopathy

• Ohtahara syndrome

• Benign familial neonatal seizures

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Early Myoclonic EncephalopathyEarly 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

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3 months later

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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

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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

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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

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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

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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

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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

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18Awake

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

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Hypsarrhythmia with focal slowing (Left temporo-occipital FCD )

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

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Ictal- Generalised sharpwaves/slow waves with attenuation

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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

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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

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• EEGs normal ; later generalized epileptic photosensitivity

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

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GEFS +SCN1A mutations

EM-AS

DRAVETs SIGEI

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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

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Migrating seizures of infantileMalignant migrating partial epilepsy of infancy

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Migrating seizures of infantile

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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

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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

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Ictal Semiology

Focal facial sensorimotor

Oro-pharyngo-laryngeal

Hyper salivation

Speech arrest

70% nocturnal

60% retained awareness

Lasts 1-2 min

Sec. Generalized- 30-50%

Clonic upperlimb

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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 ++

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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

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Epileptic Encephalopathy of Late Childhood

A spectrum of diseases

1. Landau- Kleffner syndrome2. CSWS Syndrome

• Gradual cognitive/behavior deterioration

• Acquired language impairment

• Seizures

• Dramatic activation of epileptiform abnormalities in slow wave sleep

LKS CSWS

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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

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LKS Vs Epilepsy with CSWS

» 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

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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

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Lennox Gastaut Syndrome

• Polymorphic seizuresTonic Seizures - Commonest Atypical absences – 2/3rd of patients Atonic seizures (Drop attacks)Myoclonic jerks

• Cognitive and behavioural abnormalities

• EEG Slow spike and wave, Paroxysms of fast activity

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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

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EVOLUTION OF SYNDROMES

OTAHARA’S (neonate)

WEST (infant)

LENNOX GASTAUT (toddler)

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

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Epileptic spasms a few months laterHYPSARRYTHMIA MODIFIED BY SLEEP

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

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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

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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

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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

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OIRDA

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

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Epilepsy with Myoclonic Absences

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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

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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

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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

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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

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Reflex Epilepsies

• Reading Epilepsy

• Idiopathic photosensitive occipital epilepsy

• Startle Epilepsy

• Eyelid Myoclonia with absences (Jeavons Syndrome)

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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

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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

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Jeavons Syndrome

• Age group : 6-8years

• F>M

• Eyelid myoclonia with and without absences

• Eye closure induced seizures or EEG paroxysms

• Photosensitivity

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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

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THANK YOU