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

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

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

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

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

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

3 months later

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

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

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

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

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

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

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

Hypsarrhythmia with focal slowing (Left temporo-occipital FCD )

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

Ictal- Generalised sharpwaves/slow waves with attenuation

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

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

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

EM-AS GEFS + SCN1A mutations DRAVETs SIGEI

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

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

Migrating seizures of infantile

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

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 Let me quickly run through some of the common apparently benign epileptic syndromes in childhood adolescence. The first and foremost

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

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

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

Epileptic Encephalopathy of Late Childhood 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 LKS CSWS

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

LKS Vs Epilepsy with CSWS 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

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

Lennox Gastaut Syndrome Polymorphic seizures Tonic 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

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

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

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

Epileptic spasms a few months later HYPSARRYTHMIA MODIFIED BY SLEEP

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

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

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

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

OIRDA

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

Epilepsy with Myoclonic Absences

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

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

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

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

Reflex Epilepsies Reading Epilepsy Idiopathic photosensitive occipital epilepsy Startle Epilepsy Eyelid Myoclonia with absences (Jeavons Syndrome)

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

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

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

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

THANK YOU