3. Definition
Seizure (Convulsion)
• Clinical manifestation of synchronised
electrical discharges of neurons
Epilepsy
• Present when 2 or more unprovoked
seizures occur at an interval greater than 24
hours apart
4. Definition
Provoked seizures
Seizures induced by somatic disorders
originating outside the brain
E.g. fever, infection, syncope, head trauma,
hypoxia, toxins, cardiac arrhythmias
5. Definition
Status epilepticus (SE)
Continuous convulsion lasting longer than 30
minutes OR occurrence of serial convulsions
between which there is no return of consciousness
Idiopathic SE
Seizure develops in the absence of an underlying
CNS lesion/insult
Symptomatic SE
Seizure occurs as a result of an underlying
neurological disorder or a metabolic abnormality
6. Aetiology of seizures
Epileptic
Idiopathic (70-80%)
Cerebral tumor
Neurodegenerative disorders
Neurocutaneous syndromes
Secondary to
Cerebral damage: e.g. congenital infections,
HIE, intraventricular hemorrhage
Cerebral dysgenesis/malformation: e.g.
hydrocephalus
8. Aetiology of Status Epilepticus
Prolonged febrile seizure
Most common cause
Idiopathic status epilepticus
Non-compliance to anti-convulsants
Sudden withdrawal of anticonvulsants
Sleep deprivation
Intercurrent infection
Symptomatic status epilepticus
Anoxic encephalopathy
Encephalitis, meningitis
Congenital malformations of the brain
Electrolyte disturbances, drug/lead intoxication,
extreme hyperpyrexia, brain tumor
9. Pathophysiology
Still unknown
Some proposals:
Excitatory glutamatergic synapses
Excitatory amino acid neurotransmitter
(glutamate, aspartate)
Abnormal tissues — tumor, AVM, dead area
Genetic factors
Role of substantia nigra and GABA
10. Pathophysiology
Excitatory glutamatageric synapses
And, excitatory amino acid
neurotransmitter (glutamate, aspartate)
These are for the neuronal excitation
In rodent models of acquired epilepsy and in human
temporal lobe epilepsy, there is evidence for enhanced
functional efficacy of ionotropic N-methyl-D-aspartate
(NMDA) and metabotropic (Group I) receptors
Chapman AG. Glutatmate and Epilepsy. J Nutr. 2000 Apr;
130(4S Suppl): 1043S-5S
11. Pathophysiology
Abnormal tissues — tumor, AVM, dead
area
These regions of the brain may promote
development of novel hyperexcitable
synapses that can cause seizures
12. Pathophysiology
Genetic factors
At least 20 %
Some examples
Benign neonatal convulsions--20q and 8q
Juvenile myoclonic epilepsy--6p
Progressive myoclonic epilepsy--21q22.3
13. Pathophysiology
Role of substantia nigra
Studies with 2-deoxyglucose indicate that a marked
increase in metabolic activity in SN is a common feature
of several types of generalized seizures; it is possible
that some of this increased activity is associated with
GABAergic nerve terminals that become activated in an
attempt to suppress seizure spread.
Because GABA has been shown to inhibit nigral
efferents, it is likely that GABA terminals inhibit nigral
projections that are permissive or facilitative to seizure
propagation
From Gale K. Role of the substantia nigra in GABA-
mediated anticonvulsant actions. Adv
Neurol.1986;44:343-364
14. Pathophysiology
Premature brain
It is more susceptible to specific seizures than is
the brain in older children and adults
Kindling
Repeated subconvulsive stimulation (e.g. to the
amygdala) will lead to generalized convulsion
This may explain the development of epilepsy
after injury to the brain
One temporal lobe seizure -> contralateral lobe
16. Seizures
Partial
– Electrical discharges in a
relatively small group of
dysfunctional neurones in
one cerebral hemisphere
– Aura may reflect site of
origin
– + / - LOC
Generalized
– Diffuse abnormal
electrical discharges
from both
hemispheres
– Symmetrically
involved
– No warning
– Always LOC
17. Simple Complex
Partial Seizures
1. w/ motor
signs
2. w/ somato-
sensory
symptoms
3. w/ autonomic
symptoms
4. w/ psychic
symptoms
1. simple
partial --> loss
of
consciousnes
s
2. w/ loss of
consciousnes
s at onset
Secondary
generalized
1. simple partial
--> generalized
2. complex partial
--> generalized
3. simple partial
--> complex partial
--> generalized
18. Simple partial seizures
with motor signs
Focal motor w/o march
Focal motor w/ march
Versive
Postural
Phonatory
19. Simple partial seizures
with motor signs
Sudden onset from
sleep
Version of trunk
Postural
Left arm bent
Forcefully stretched
fingers
Looks at watch
Note seizure
21. Simple partial seizures
with sensory symptoms
Vertiginous symptoms
“Sudden sensation of
falling forward as in
empty space”
No LOC
Duration: 5 mins
23. Simple partial seizures
with autonomic symptoms
Stiffness in L cheek
Difficulty in articulating
R side of mouth is dry
Salivating on the L
side
Progresses to tongue
and back of throat
25. Simple partial seizure
with pyschic symptoms
Dysmnesic symptoms
“déjà-vu”
Affective symptoms
fear and panic
Cognitive
Structured
hallucination
living through a scene
of her former life again
26. Complex Partial Seizures
Simple partial onset followed by
impaired consciousness
with or without automatism
With impairment of consciousness at
onset
with impairment of consciousness only
with automatisms
27. Simple Partial Seizures
followed by Complex Partial
Seizures
Seizure starts from
awake state
Impairment of
consciousness
Automatisms
lip-smacking
right leg
28. Complex Partial Seizures with
impairment of consciousness
at onset
Suddenly sit up
Roll about with
vehement
movement
29. Partial Seizures evolving to
Secondarily Generalised
Seizures
Simple Partial Seizures to Generalised
Seizures
Complex Partial Seizures to Generalised
Seizures
Simple Partial Seizures to Complex Partial
Seizures to Generalised Seizures
30. Simple Partial Seizures to
Generalised Seizures
Turns to his R with
upper body and
bends his L arm
Stretches body
LOC
Tonic-clonic seizure
Relaxation phase
Postictal sleep
31. Simple Partial Seizures to
Complex Partial Seizures to
Generalised Seizures
Initially unable to
communicate but
understands
Automatism
Smacking
Hand-rubbing
Abolished
communication
Generalised tonic-
clonic seizure
33. Absence seizures
Sudden onset
Interruption of ongoing activities
Blank stare
Brief upward rotation of eyes
Duration: a few seconds to 1/2 minute
Evaporates as rapidly as it started
35. Myoclonic seizures
Sudden, brief, shock-like
Predominantly around the hours of going to
or awakening from sleep
May be exacerbated by volitional
movement (action myoclonus)
37. Clonic seizures
Repetitive biphasic
jerky movements
Repetitive vocalisation
synchronous with
clonic movements of
the chest (mechanical)
Venous injection of
diazepam
Passes urine
38. Tonic seizures
Rigid violent muscle contraction
Limbs are fixed in strained position
patient stands in one place
bends forward with abducted arms
deep red face
noises - pressing air through a closed mouth
39. Tonic seizures
Elevates both hands
Extreme forward
bending posture
Keeps walking
without faling
Passes urine
40. Tonic-clonic seizures
(grand mal)
Tonic Phase
Sudden sharp tonic
contraction of respiratory
muscle: stridor / moan
Falls
Respiratory inhibition
cyanosis
Tongue biting
Urinary incontinence
Clonic Phase
Small gusts of grunting
respiration
Frothing of saliva
Deep respiration
Muscle relaxation
Remains unconscious
Goes into deep sleep
Awakens feeling sore,
headaches
41. Tonic-clonic seizures
Tonic stretching of
arms and legs
Twitches in his face
and body
Purses his lips and
growls
Clonic phase
43. Epilepsy syndrome
Epilepsy syndromes may be classified
according to:
Whether the associated seizures are partial or
generalized
Whether the etiology is idiopathic or
symptomatic/ cryptogenic
Several important pediatric syndromes can
further be grouped according to age of onset and
prognosis
EEG is helpful in making the diagnosis
Children with particular syndromes show
signs of slow development and learning
difficulties from an early age
44. Category Localization-related Generalized
Idiopathic Benign epilepsy of childhood with
centrotemporal spikes
(benign rolandic epilepsy)
Benign occipital epilepsy
Benign myoclonic epilepsy in infancy
Childhood absence epilepsy
Juvenile absence epilepsy
Juvenile myoclonic epilepsy
Symptomatic (of
underlying structural
disease)
Temporal lobe
Frontal lobe
Parietal lobe
Occipital lobe
Early myoclonic encephalopathy
Cortical dysgenesis
Metabolic abnormalities
West syndrome
Lennox-Gastaut syndrome
Cryptogenic Any occurrence of partial seizures
without obvious pathology
Epilepsy with myoclonic absences
West syndrome (with unidentified
pathology)
Lennox-Gastaut syndrome (with
unidentified pathology)
Table 1. Modified ILAE Classification of Epilepsy Syndromes
45. Special syndromes Febrile convulsions
Seizures occurring only with toxic or metabolic
provoking factors
Neonatal seizures of any etiology
Acquired epileptic aphasia (Landau-Kleffner
syndrome)
Table 1. Modified ILAE Classification of Epilepsy Syndromes
(cond’)
46. Three most common epilepsy syndromes:
1. Benign childhood epilepsy
2. Childhood absence epilepsy
3. Juvenile myoclonic epilepsy
Three devastating catastrophic epileptic
syndromes:
1. West syndrome
2. Lennox-Gastaut syndrome
3. Landau Kleffner Syndrome
47. Benign childhood epilepsy with
centrotemporal spike
(Benign Rolandic Epilepsy)
1. Typical seizure affects mouth, face, +/- arm.
Speech arrest if dominant hemisphere,
consciousness often preserved, may generalize
especially when nocturnal, infrequent and easily
controlled
2. Onset is around 3-13 years old, good respond to
medication, always remits by mid-adolescence
48. Childhood absence epilepsy
1. School age ( 4-10 years ) with a peak age of onset at 6-7
years
2. Brief seizures, lasting between 4 and 20 seconds
3. 3Hz Spike and wave complexes is the typical EEG abnormality
4. Sudden onset and interruption of ongoing activity, often with a
blank stare.
5. Precipitated by a number of factors i.e. fear, embarrassment,
anger and surprise. Hyperventilation will also bring on
attacks.
Juvenile myoclonic seizure
1. Around time of puberty
2. Myoclonic ( sudden spasm of muscles ) jerks → generalized
tonic clonic seizure without loss of consciousness
3. Precipitated by sleep deprivation
49. West’s syndrome (infantile spasms)
Triad:
1. infantile spasms
2. arrest of psychomotor development
3. hypsarrhythmia
Spasms may be flexor, extensor, lightning, nods,
usually mixed. Peak onset 4-7 months, always before 1
year.
Lennox-Gastaut syndrome
Characterized by seizure, mental retardation and
psychomotor slowing
Three main type:
1. tonic
2. atonic
3. atypical absence
Landau- Kleffner syndrome ( acquired aphasia )
50. Diagnosis in epilepsy
Aims:
Differentiate between events mimicking
epileptic seizures
E.g. syncope, vertigo, migraine, psychogenic
non-epileptic seizures (PNES)
Confirm the diagnosis of seizure (or
possibly associated syndrome) and the
underlying etiology
51. Diagnosis in epilepsy
Approach:
History (from patient and witness)
Physical examination
Investigations
52. History
Event
Localization
Temporal relationship
Factors
Nature
Associated features
Past medical history
Developmental history
Drug and immunization history
Family history
Social history
53. Physical Examination
General
esp. syndromal or non-syndromal
dysmorphic features, neurocutaneous
features
Neurological
Other system as indicated
E.g. Febrile convulsion, infantile spasm
54. Investigations
I. Exclusion of differentials:
Bedside: urinalysis
Haematological: CBP
Biochemical: U&Es, Calcium, glucose, ABGs
Radiological: CXR, CT head
Toxicological: screen
Microbiological: LP
(Always used with justification)
55. Investigations
II. Confirmation of epilepsy:
Dynamic investigations : result changes
with attacks
E.g. EEG
Static investigations : result same between
and during attacks
E.g. Brain scan
56. Electroencephalography
(EEG)
EEG indicated whenever epilepsy
suspected
Uses of EEG in epilepsy
Diagnostic: support diagnosis, classify
seizure, localize focus, quantify
Prognostic: adjust anti-epileptic treatment
61. Electroencephalography
(EEG)
Note:
Normal in 10-20% of epileptic patients
Background slowed by:
AED, diffuse cerebral process, postictal state
Artifact from:
Eye rolling, tremor, other movement, electrodes
Interpreted in the light of proximity to
seizure
63. Structural Neuroimaging
Who should have a structural
neuroimaging?
Status epilepticus or acute, severe
epilepsy
Develop seizures when > 20 years old
Focal epilepsy (unless typical of benign
focal epilepsy syndrome)
Refractory epilepsy
Evidence of neurocutaneous syndrome
64. Structural Neuroimaging
Modalities available:
Magnetic Resonance Imaging (MRI)
Computerized Tomography (CT)
What sort of structural scan?
MRI better than CT
CT usually adequate if to exclude large tumor
MRI not involve ionizing radiation
I.e. not affect fetus in pregnant women (but nevertheless
avoided if possible)
65. Functional Neuroimaging
Principles in diagnosis of epilepsy:
When a region of brain generates seizure,
its regional blood flow, metabolic rate and
glucose utilization increase
After seizure, there is a decline to below
the level of other brain regions throughout
the interictal period
66. Functional Neuroimaging
Modalities available:
Positron Emission Tomography (PET)
Single Photon Emission Computerized
Tomography (SPECT)
Functional Magnetic Resonance Imaging (fMRI)
Mostly used in:
Planning epilepsy surgery
Identifying epileptogenic region
Localizing brain function
69. Education & Support
Information leaflets and information
about support group
Avoidance of hazardous physical
activities
Management of prolonged fits
Recovery position
Rectal diazepam
Side effects of anticonvulsants
70. Anticonvulsants
Suppress repetitive action potentials in
epileptic foci in the brain
Sodium channel blockade
GABA-related targets
Calcium channel blockade
Others: neuronal membrane
hyperpolarisation
71. Anticonvulsants
Cabamazepine
Phenytoin
Valproic acid
Tonic-clonic and partial
Ethosuximide
Valproic acid
Clonazepam
Absence seizures
Valproic acid
Clonazepam
Myoclonic seizures
Diazepam
Lorazepam
Short term
control
Phenytoin
Phenobarbital
Prolonged
therapy
Status Epilepticus
Corticotropin
Corticosteroids
Infantile Spasms
Drugs used in seizure disorders
73. Medical Intractability
No known universal definition
Risk factors
High seizure frequency
Early seizure onset
Organic brain damage
Established after adequate drug trials
Operability
74. Surgery
Curative
Catastrophic unilateral or secondary
generalised epilepsies of infants and young
children
Sturge-Weber syndrome
Large unilateral developmental abnormalities
Palliative
Vagal nerve stimulation
75. Surgical Outcome
Medical Intractability
A well-localised epileptogenic zone
EEG, MRI
Low risk of new post-operative deficits
76. References
1. Stedman’s Medical Dictionary.
2. MDConsult: Nelson’s textbook.
3. Illustrated Textbook of Pediatrics.
4. Video atlas of epileptic seizures – Classical
examples, International League against
epilepsy.
5. Guberman AH, Bruni J, 1999, Essentials of
Clinical Epilepsy, 2nd
edn. Butterworth
Heinemann.
6. Manford M, 2003, Practical Guide to
Epilepsy, Butterworth Heinemann.
Hinweis der Redaktion
Prolonged febrile seizure:
-lasting for more than 30min, particularly in a child younger than 3, is the most common cause of SE
Sudden withdrawal of anticonvulsants:
-Especially benzodiazepines and barbiturates
Simple partial
In simple partial seizures, consciousness is not impaired.
Patients can present with motor, somatosensory, special sensory, autonomic or psychic symptoms
complex
A complex partial seizure describes a seizure where consciousness is impaired.
A partial seizure may begin with a simple seizure, conversely, its onset may coincide with the impairment of consciousness.
It may be presented with or without an aura.
2ndary generalized
Partial sezure evolve to secondarily generalized seizures
May be gen. Tonic-clonis, tonico or clonic
Focal motor may remain strictly focal OR
they may spread to contiguous cortical areas producing a sequential
involvement of body parts in an epileptic march - Jacksonian seizure
Versive : head turning to one side usually contraversive to the discharge
Simple partial seizure
with versive motor signs and postural motor signs
usually arising from sleep; version of trunk to R
L arm bent at elbow, finger forcefully stretched
R arm beats on arm of chair to warn the nurse
tonic contraction of face and eyes
jerking of head and L shoulder
turns back to normal position
support head with R hand
look at watch for note seizure in calender
Areas of cortex subserving sensory function, described as pins and needles / numbness
Visual: flashing lights - structured visual hallucinatory phenomena e.g. persons, scenes.
Auditory: crude aud sensations - highly integrated functions e.g. music
Olfactory: unpleasant odours
Gustatory sensations: pleasant / odious taste often described as metallic
Vertiginous: sensations of falling in space, floating
borborygmi
Psychic: disturbance of higher mental function
Dysmnesic symptoms: deja-vu or jamais-vu,
forced thinking - panoramic vision ( a rapid recollection of episodes from his/her past life)
Cognitive: dreamy states, distorsions of time sense. Detachment or depersonalisation
Affective: Anger and Fear which is apparently unprovoked and abates rapidly
Talking b4 sezure
take off spectacles and tell others a seizure is coming
turn to the R with upper body and bends his L arm
“it’s getting stronger”
he turns to his L , stretches his body, loses consciousness
the seizure develops into a tonic-clonic seizure with relaxation a=phase and postictal sleep
Begins with an epigastric rising sensation, which the patient signals
later, unable to speak, waving her L hand, can’t communicate
followed by smacking and hand-rub
Generalized seizure:
Atonic1: lack of normal tone
Tonic1: under continuous tension
Clonic1: rhythmic contractions and relaxations of a muscle in rapid succession
Myoclonic1: single or repetitive sudden twitching or spasm of a muscle or a group of muscles
Slight impairment of mental performance:
Heard what was spoken to her before the seizure stopped, but has probably not understood it qte right
“are you there” and “is it there” sound very close to each other in Danish
Usually:
patient stands in one place
bends forward with abducted arms
deep red face
noises - pressing of air through a closed mouth
EEG show generalized sharp waves
spikes decrease in frequency
Idiopathic (with age-related onset) – normal neuro exam, development and neuroimaging, typically nocturnal, usually stop in adolescence, family history 40%
1. Benign childhood epilepsy with centrotemporal spike (aka benign rolandic epilepsy)
a. Age of onset 2-13 yrs, accounts for 11.5-25% of childhood epilepsy (autosomal dominant with variable penetrance). Always remits by mid-adolescence.
b. Typical seizure affects mouth, face, +/- arm. Speech arrest if dominant hemisphere, consciousness often preserved, may generalize especially when nocturnal, infrequent and easily controlled
c. Interictal EEG normal background, midtemporal and central high-amplitude spikes and sharp waves, increased in sleep, can be unilateral (less often) or bilateral but independent (more often). Ictal EEG shows unilateral sharps which can occasionally be bilateral. Sharps can be occipital in <5 yo.
Prognosis related to underlying cause, response to treatment. ACTH or steroids
West
Prognosis related to underlying cause, response to treatment. ACTH or steroids
Lennox-Gastaut syndrome
Three main type:
tonic
atonic
atypical absence
Begins age 1-8 yo, seizures can be tonic-axial, atonic, absence, myoclonic, GTC, usually frequent sz, frequent status epilepticus, seizures difficult to control. EEG abnormal background, slow spike and wave (<3Hz), often multifocal abnormalities. Usually has mental retardation.
Localization: aspects involved e.g. motor, sensory? Any specific site e.g. one limb involved, or generalized involvement?
Temporal relationship: number of episode? Diurnal pattern? Duration? Onset and offset? Progression? Persistency?
Factors: precipitating?
Nature: consciousness impaired? Type of sensory/ motor/ psychic/ emotional disturbances observed/ experienced?
Associated features: Prodrome? Aura? Postictal state? Colour of patient? Focal neurological sign?
Na channel blockade: phenytoin, carbamazepine, lamotrigine
GABA-related targets: benzodiazepines interact with specific receptors on GABAa receptor-chloride ion channel macromolecular complex
Ca channel blockade: ethosuxamide inhibits low-threshold Ca currents especially in thalamic neurons that act as pacemakers to generate rhythmic cortical discharge
Other mechanisms:
Valproic acid - neuronal membrane hyperpolarisation possibly by enhancing K channel permeability
Infantile spasms: corticotropin and corticosteroids are commonly used but cause cushingoid side effects.
Neural tube defects (spina bifida) associated with valproic acid
Fetal hydantoin syndrome - phenytoin
Overdosage: most of the commonly used anticonvulsants are CNS depressants - respiratory depression
Life threatening toxicity
fatal hepato. - valproic acid
greatest risk to children <2 yrs of age and patients taking multiple anticonvulsant drugs
Lamotrigin - skin rashes and life-threatening Stevens Johnsons syndrome
Abrupt withdrawal - increased seizure frequency and severity
Intractability can be established after:
2-3 of the established newer first and second line AED, as monotherapy at least one in combination
max tolerated dose
High seizure frequency: daily / weekly episode
brain damage: the more severe the brain damage, the greater the likelihood of seizure persistence
Assess operability using imaging studies
Large unilateral developmental abnormalities such as cortical dysplasias and porencephalic cysts
