1. Electro clinical epileptic syndrome
ZAKI NOAH HASAN
Professor of neurology
ALKINDI COLLEGE OF MEDICIN

2. 'Teacher, I brought my son to you, because he has an evil spirit in him and cannot talk. Whenever the spirit attacks him, it throws him to the ground, and he foams at the mouth, grits his teeth and becomes stiff all over.' (Mark 9, 17-18)

3. localization-related
seizure types
idiopathic
idiopathic
generalized seizures
localization-related
symptomatic
cryptogenic
cryptogenic
epileptic Syndromes

4. Classification Electro clinical syndromes Epilepsy constellations
Epilepsies secondary to specific structural or metabolic cause
Epilepsies of unknown cause

5. EPILEPSY SYNDROMES
Recognized Disorder identifiable on the basis of
Typical age onset,
Clusters of signs and symptoms occurring together
Seizure types
Cognitive and developmental features
EEG characteristics
Specific provoking or triggering factors
Patterns of seizure occurrence with respect to sleep

7. Epilepsy constellations
Entities which are not syndromes per se but represent clinically distinctive collections of features
Age of onset is variable and not considered as defining feature
Often treated surgically
T L E with hippocampal sclerosis
Gelastic seizures with hypothalamic hamartoma
Rasmussen syndrome
Epilepsies secondary to specific structural or metabolic cause
Defined on the etiology and less specificity on localization eg focal cortical dysplasia in the temporal lobe

9. < 44 weeks of gestational age
Neonatal period:
< 44 weeks of gestational age
1--Benign familial neonatal epilepsy BFNE:
2--Early myoclonic encephalopathy
EME
3--Early Infantile Epileptic Encephalopathy (EIEE)
Ohtahara syndrome

10. Early Infantile Epileptic Encephalopathy (EIEE) or Ohtahara Syndrome (OS)
Intractable tonic spasms seizure occurring with or without clustering
EEG : persistent interictal bursts suppression (SB) pattern observed in both waking and sleeping states
causes : symptomatic causes : Several brain malformations, neuronal migration disorders and metabolic Disorder
cryptogenic causes : the aristaless-related homeobox (ARX) and the syntaxin binding protein 1 (STXBP1) genes
Prognosis is very poor with severe drug-resistance and psychomotor Retardation
evolution into the West syndrome (reported in 75% of cases)

11. EEG pattern of suppression burst.

12. Benign Familial Neonatal (BFNS)
autosomal-dominant, benign familial epilepsy syndrome
BFNS is linked to mutations in KCNQ2 and KCNQ3 genes
unprovoked and brief cluster [20 – 30 times per day ] of Focal, multifocal, or generalized tonic-clonic convulsions
occurring within the first days of life and frequently flowing into status epilepticus.
No specific EEG trait
Seizures disappear spontaneously within 2 months of life.
However about 10%-15% of children with BFNS develop seizures later

13. Benign Idiopathic Neonatal Seizures
Early Myoclonic Encephalopahty (EME)
Seizures typically begin on the fifth day of life or “fifth day fits”
Partial clonic seizures that migrate, increase in frequency and culminate in status epilepticus
No specific EEG features
no family history
Children have normal neurodevelopment
No increased risk of seizure recurrence
associated primarily to metabolic disorders
Seizures type : fragmentary myoclonus
EEG in EME shows a suppression-burst pattern

14. Infancy: 1 < year Epilepsy of infancy with migrating focal seizures
West syndrome
MEI
Benign infantile epilepsy
1 < year
Benign familial infantile epilepsy
Dravet syndrome
Myoclonic encephalopathy in non progressive disorders
FS+ (can start in childhood)

15. West syndrome (WS), also called Infantile Spasms (IS) or Salaam Spams
incidence which is estimated about 1, 6- 4, 2 per 10,000 live births
Triad that consists of
seizures (so-called IS: generally consisting of, sudden, bilaterally and symmetrical, flexor, extensor or mixed type, spasms of the neck, trunk and extremities), [Delay in diagnosis is often considerable; parents and pediatricians think movements are due to colic; cry after spasms]
characteristic EEG (hypsarrhytmia)
psychomotor retardation.
AGE : 1-5 years
TYPES : seizures are heterogeneous and occur at awakening and during crying

16. CAUSES : symptomatic, cryptogenetic and idiopathic two genes, ARX and STK9, in patients with X-linked familial West syndrome
Tuberous sclerosis is a major cause of infantile spasms (up to 25%)Other etiologies include: lissencephaly, Sturge-Weber, HIE, meningitis, and inborn errors of metabolism
GVG is the drugs of first choice for patients with tuberous sclerosis & Focal Cortical Dysplasia (FCD), The efficacy of GVG is increased with high doses ( mg/Kg/day) compared with the standard doses ( mg/Kg/day)
A challenge with a 100mg of IV pyridoxine should be considered in idiopathic cases

17. THE HIGH-AMPLITUDE, DISORGANIZED SLOW ACTIVITY WITH MULTIFOCAL SPIKES
an electrodecremental response. This sort of electrodecremental event may be associated with a clinical spasm
“random high voltage slow waves and spikes, that vary from moment to moment in duration and in location: at the onset, they appear to be focal and then they seem to originate from multiple foci; in few cases the spike discharge becomes generalized

18. Genetic Epilepsy with Febrile Seizure Plus (GEFS+)
GEFS+ is a familial autosomal-dominant epileptic syndrome with a large pattern of phenotypic variability.
Characterized by febrile and afebrile seizures
febrile seizures plus( FS+) febrile seizures above the 6th year of age
Genetic Epilepsy with Febrile Seizure Plus (GEFS+) is afebrile myoclonic, absence, atonic, or partial seizures plus ( FS+) febrile seizures (FS)
severe myoclonic epilepsy of infancy” (SMEI)represent the most severe form.

19. Spectrum of GEFS + febrile Seizures (FS)
Generalized Epilepsy with febrile seizures plus (GEFS+)
Severe Infantile Multifocal Epilepsy (SIMFE)
Severe Myoclonic Epilepsy of Infancy Borderline (SMEB)
Severe Myoclonic Epilepsy of Infancy (SMEI/Dravet Syndrome)
Epilepsy and mental retardation limited to females (EFMR/PCDH19)
Sporadic Infantile Epileptic Encephalopathy (SIEE)
Intractable Childhood Epilepsy with Generalized Tonic Clonic Seizures (ICE-GTC)

20. Etiology
Sodium channel related seizure disorders encompass a spectrum that ranges
from simple febrile seizures (FS) and genetic epilepsy with febrile seizures plus (GEFS+) at the mild end
to Dravet syndrome (Ds) at the severe end

21. Severe Myoclonic Epilepsy of Infancy (SMEI) Dravet Syndrome
incidence estimated between 1:20,000 and 1:40,000,
representing 3-8%of patients having their first seizure before age one
affect an equal number of boys and girls 
Seizures start 4 months and 10 years, with mean onset of 2 years
Prior to onset of afebrile seizures, GEFS+ can be difficult to distinguish from febrile seizure
Careful family history is important

22. autosomal dominant with 60-80% penetrance
Within families multiple phenotypes with variable severity exist
an epileptic encephalopathy starting during the first year of life, especially around the 6th month, with recurrent and long-lasting febrile seizures, also as febrile status epilepticus.
Drug-resistant myoclonic, complex partial, and atypical absence seizures can appear after the 12 months of life.

23. Dravet Syndrome
Begins in the first year of life in previously well infant
Generalized or focal clonic seizure is often prolonged
Onset frequently triggered by fever, infection, vaccination or warm bath
Progression to further recurrent prolonged focal seizures with and without fever

24. prolonged seizure which is often associated with vaccines
an infant presents with myoclonic jerks after the first prolonged seizure that occurs before the first birthday, Ds should be considered early in the differential diagnosis
After age 2, they may lose developmental milestones or do not progress as quickly as they get older and have more seizures.
Around 6 years old, cognitive problems in some children may stabilize or may start improving.
However, most children with Dravet syndrome have some degree of developmental disability that persists.

25. Patients with Ds have similar symmetric facial features including large, wide-set eyes; a flat nasal bridge; full lips; low facial muscle tone; and an oval face with a small chin. This “cherubic look”continues into adulthood. Multi-national dysmorphology studies are ongoing.

26. Sodium channel blockers including phenytoin, fosphenytoin, carbamazepine, oxcarbazipine, lamotrigine, lascomide and rufinamide are not recommended for acute or chronic management of Ds.
These drugs may worsen the seizures cased by sodium channel mutations producing loss of channel function.
Selective GABA reuptake inhibitor/GABA-T inhibitors including vigabatrin and tiagabine often exacerbate myoclonic seizures and may worsen overall seizure control

27.  Stiripentol + clobazam + valproic acid is the most well studied and efficacious regimen for children with Ds. 
Topirimate, valproic acid, clonazepam, clobazam, levetriacetam, potassium bromide, zonisamide and the ketogenic diet in various combinations have also shown efficacy in Ds
Stiripentol is not not indicated as monotherapy.
Caution should be exercised when adding stiripentol to clobazam and valproic acid due to significant increases in active drug and metabolites which may lead to toxicity

28. prognosis
• Expressive and receptive language impairment • Pronation of feet that often goes unnoticed and leads to painful orthopedic conditions • Ataxia and gait abnormalitiesa [crouched gait] • Low muscle tone • Chronic infection and low humoral immunity • Growth and nutrition abnormalities including malnutrition • Dysautonomia • Autistic spectrum, attention deficit, and other behavioral disorders including psychosis • Sleep disorders

29. case
4 months girl referred with Seizures lasting more than 10 minutes, seizures occurring on one side of the body immediately after warm water bath
at 6 month the infant developed second seizure after vaccine administration .
Infants eventually develop other seizure types including atypical absence, eyelid myoclonia and non-convulsive seizures

30. absences starting from a few months to 4 years of age,
Early-Onset Absence Epilepsy (EOAE)
absences starting from a few months to 4 years of age,
associated with other neurological disorders (other types of seizures, developmental delay, and movement disorders)
normal early psychomotor development,
good AEDs seizure control and normal intellectual outcome
Mutations in three different genes GABRG2 gene have been described in patients with febrile seizures and CAE and mutations in SCN1B and SCL2A1
SCL2A1 is responsible for the GLUT1 deficiency syndrome (infantile-onset epilepsy with heterogeneous type of seizures, complex movement disorders, ataxia, intellectual disability, macrocephaly, and hypoglycorrhachia)

31. the 2ed most common types of benign childhood partial seizures
Panayiotopoulos Syndrome
the 2ed most common types of benign childhood partial seizures
age at onset is between 1 and 14 years (with 13% in the youngest age group of 3-6 years)
most individuals have their first seizure around the age of 5 ys.
This syndrome (affecting males and females almost equally
seizures, often prolonged, with predominantly autonomic symptoms, and by Seizures occur during nocturnal sleep, particularly the early part of sleep, or brief daytime naps
Unilateral deviation of the eyes
vomiting is the commonest ictal manifestation
pallor, mydriasis, miosis, cardiorespiratory and thermoregulatory alterations, incontinence of urine and/or faeces, hypersalivation and modifications of intestinal motility

32. The duration of the seizures is usually longer than 10 min
Approximately (44%) of them last from 30 min to many hours, developing an autonomic status epilepticus
No neurological or mental abnormalities
Interictal EEG shows occipital spikes (70%) although multifocal spikes with high amplitude sharp-slow wave complexes at various locations represent the most common EEG feature

33. Benign occipital epilepsy
Benign occipital epilepsy. Note the independent, bi-occipital sharp and slow wave complexes with eyes closed

35. Jeavons syndrome (eyelid myoclonia with Absences)
 reflex idiopathic generalized epilepsy (IGE) syndrome with well-defined clinico-EEG manifestation
Prevalence ~3% of adults with epileptic disorders and 13% among IGEs with absences.
Age at onset Range is 2 to 14 years; peak at 6 to 8 years.
Sex 2-fold female preponderance.
Neurological and mental state Normal.
Etiology Genetically determined
Negative family and past history

36.  Triad of
brief (3–6 s) eyelid myoclonia with and without absences, These are mainly precipitated by closing of the eyes and lights.
eye-closure-induced seizures, EEG paroxysms, or both,
photosensitivity [Contrary to other forms of photosensitive epilepsies that are sensitive only to flickering lights, Jeavons syndrome are sensitive to bright, non-flickering lights]

37. Eyelid myoclonia with absences (Jeavons syndrome)
. Eyelid myoclonia with absences (Jeavons syndrome). Twelve-year-old girl with eyelid myoclonia associated with absence seizures and a rare, generalized tonic-clonic seizure, responsive to valproic acid. Note the generalized polyspikes induced by eye closure

38. Prognosis Jeavons syndrome is a lifelong disorder,
Men have a better prognosis than women.
There is a tendency for photosensitivity to disappear in middle age,
eyelid myoclonia persists. It is highly resistant to treatment and occurs many times a day

39. Myoclonic Astatic [ atonic ]Epilepsy of Doose
affecting 1:10,000
Presents in previously neurologically healthy preschool-aged children
Multiple seizure types including generalized tonic clonic, myoclonic, absence, atonic, myoclonic, myoclonic atonic
atonic seizures is the most prominent
Outcome and course are variable – complete remission to intractable epilepsy with poor cognitive outcome
EEG demonstrates 2-3Hz spike and wave discharges
Up to 32% of children have a family history of epilepsy

40. Myoclonic astatic epilepsy (Doose syndrome)
Myoclonic astatic epilepsy (Doose syndrome). Five-year-old boy with generalized tonic-clonic seizures and myoclonic-astatic seizures. Note the generalized spike-and-wave discharge, with a frontal predominance, with a background of 6 Hz.

41. Lennox- Gastaut Syndrome
a form of symptomatic generalized epilepsy
Prematurity, perinatal injury and metabolic diseases of infancy
onset between 2 and 8 years of age
Males > females
characterized by atonic, or astatic seizures (i.e., falling attacks), minor motor, tonic-clonic, and partial seizures
progressive intellectual impairment
a distinctive, slow (1- to 2-Hz) spike-and-wave EEG pattern during sleep and on awaking
Often it is preceded in earlier life by infantile spasms

42. Lennox Gastaut Syndrome
Tonic Seizures:
Most characteristic – prerequisite
Flexor movement of the head and trunk with apnea preceded by brief cry (axial)
Abduction, elevation of limbs, usually arms with clenching of the fists (axorhizomelic)
Sustained contraction involving most
muscles, including distal (global)

43. Slow spike and wave of Lennox-Gastaut syndrome (LGS)
Slow spike and wave of Lennox-Gastaut syndrome (LGS). Thirty-six-year-old man with LGS. Note the bilaterally synchronous Hz spike-and-wave discharges

44. Landau Kleffner (LKS)
is a rare syndrome of unknown etiology (more common in the children between 5 and 7 years age)
suddenly & a prolonged period of loss of language skills in children previously normal
aphasia can be primarily receptive or expressive
Verbal auditory agnosia, that consists of a loss of verbal comprehension, which may be confused as a acquired deafness
followed by gradual deterioration also in verbal production and, finally, mutism
types of seizures,which include episodes of eye blinking or ocular deviation,head drop and minor automatisms with secondary generalization. In other cases, seizures are focal or tonic clonic generalized seizures, typical absences, partial complex and occasionally myoclonic seizures [
if the onset is in pre-linguistic phase (onset under the age of 3-4 years) and these children can be misdiagnosed for autistic due to impaired linguistic skill
rolandic epilepsy withspeech dyspraxia, autosomal dominant: (RESDAD)

45. (LKS). Four-year-old girl with LKS
(LKS). Four-year-old girl with LKS. Language regression occurred at 3 yr of age. Note the generalized, high-amplitude, slow spike-and-wave discharge during sleep, representing electrical status epilepticus of sleep.

46. EEG shows bilateral temporal spikes or spikes waves, increasing during sleep. In these patients an awake EEG usually demonstrates normal background activity and
focal epileptiform abnormalities especially on the temporal lobes
the pattern of electrical status epilepticus during sleep (ESES or CSWS) may often be observed
The treatment of choice in LSK appears to be VPA as mono-therapy or in
combination with a benzodiazepine [ steroids and ACTH should be considered the treatment of choice especially in early onset of disease with improvement in speech abilities and EEG anomalies recovery
The prognosis of LKS is benign in most cases, although the improvement of language depends on age of onset (pre and post-linguistic onset) of the disorder and the severity of the epileptic seizures. Early onset makes the prognosis poorer with persistent language difficulties even in the adult life

47. initial period with seizures and no developmental involvement
EPILEPTIC ENCEPHALOPATHIES WITH IGS AND
CONTINUOUS SPIKE-WAVE COMPLEXES DURING SLEEP
refers to the EEG pattern (continuous spike-wave complexes exclusively during non-REM sleep, with a spike-wave index accounting for at least 80-85% of SS)
CSWS indicates both EEG features and clinical neuropsychological characteristics of this EE
initial period with seizures and no developmental involvement
intermediate period with seizures, neuropsychological regression and ESES
final period with only neuropsychological deficits
, “Pseudo-Lennox Syndrome”, firstly described by Aicard’ e Chevrie
. It was often mistaken, in the past, for LGS because of the repeated atonic falls, absences and slow-wave activity at EEG

48. Late-onset childhood occipital epilepsy (Gastaut type)
3 to 15 years with a mean around 8 years of age.
idiopathic occipital epilepsy
Seizure are purely occipital,
frequent, brief and diurnal.
They comprise simple partial seizures characterized by initial visual hallucinations (phosphenes and/or ictal blindness and illusions);
ictal or postictal migraine headaches occur in half of the patients.
Impairment of consciousness is rare unless associated with hemi-clonic or generalized convulsions
Interictal EEG recordings reveal occipital spike and wave discharges that
attenuate or disappear when the eyes are opened
The prognosis is unclear, although remission occurs in 50-60% of patients within 2-4 years from onset.

49. OIRDA. Eight-year-old girl with childhood absence epilepsy
OIRDA. Eight-year-old girl with childhood absence epilepsy. Note the high amplitude, notched, 3- to 3.5-Hz occipital activity that attenuates with eye opening

50. Childhood Absence Epilepsy
autosomal dominant pattern with incomplete penetrance
Affects Girls [between 4-10 ys] 2-5 times more likely to have absence
normal neurological exams
normal intelligence scores
Automatisms, brief clonic jerks, and loss of postural tone can also be seen
abnormalities in T-type calcium channels in the thalamic neurons
11-18% of cases precede juvenile myoclonic epilepsy

51. Drug of choice is ethosuximide (T-type calcium channel blocker) because of fewer incidence of side effects
Valproic acid is the drug of choice in patients with both absence and generalized tonic-clonic seizures
Lamictal is a safer choice for female teens

52. Juvenile Absence Epilepsy
Classic form is likely autosomal dominant and inherited and linked to 6p12-11
Onset : 10 and 16 ys
equal gender involvement
Clinical seizures absence(20%) myoclonus(100%) and generalized tonic clonic seizures (90%)
Interictal EEG, 3.5-4Hz spike and polyspike and wave usually maximal in the fronto- central regions often provoked by Photic stimulation in (30 to 90%)
Response to treatment good, but may be lifelong

53. Juvenile Myoclonic Epilepsy
Generalized Polyspike and Wave Discharge

54. seizure noted is a GTC in setting of sleep deprivation but Careful questioning will reveal a history of unnoticed myoclonic seizures and possible absence seizures in the preceding months
Seizures are precipitated by sleep deprivation, alcohol ingestion and in women, menstruation

55. Benign Childhood Epilepsy with Centrotemporal Spikes (BCECTS)
Most common form of idiopathic partial epilepsy
Although it is clearly familial, its mode of inheritance is unclear
Onset is between 4 and 10 years
Children are neurologically and cognitively normal
usually occurring after falling asleep or before awakening is typical
Seizures described as unilateral paresthesias of the face, unilateral clonic or tonic activity involving the face, speech arrest, drooling with preserved consciousness

56. EEG Findings BCECTS
Spikes are present at the midtemporal and central (Centro temporal) head region
Marked activation of spikes in drowsiness and sleep is characteristic, and 30% of cases show spikes only during sleep