Seizures & Epilepsy

MBBS IV Group C
Tutor: Prof. V. Wong
16th Feb 2004
Outline

 Definitions
 Pathophysiology
 Aetiology
 Classification
 Video demonstration
 Diagnostic approach
 Treatment
 Quiz
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
Definition

 Provoked seizures
 Seizuresinduced by somatic disorders
originating outside the brain
 E.g. fever, infection, syncope, head trauma,
hypoxia, toxins, cardiac arrhythmias
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
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
Aetiology of seizures

 Non-epileptic
 Febrile convulsions
 Metabolic
 Hypoglycemia
 HypoCa, HypoMg, HyperNa, HypoNa
 Head trauma
 Meningitis
 Encephalitis
 Poisons/toxins
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
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

Pathophysiology
 Excitatoryglutamatageric 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
Pathophysiology

 Abnormal tissues — tumor, AVM, dead

area
 Theseregions of the brain may promote
development of novel hyperexcitable synapse
that can cause seizures
Pathophysiology

 Genetic factors
 Atleast 20 %
 Some examples
 Benign neonatal convulsions--20q and 8q
 Juvenile myoclonic epilepsy--6p

 Progressive myoclonic epilepsy--21q22.3

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
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
Classification of seizures
 Seizures

Partial Generalized
– Electrical discharges in a – Diffuse abnormal
relatively small group of electrical discharges
dysfunctional neurones in from both
one cerebral hemisphere hemispheres
– Aura may reflect site of – Symmetrically
origin involved
– + / - LOC – No warning
– Always LOC
 Partial Seizures

Simple Complex Secondary

generalized
1. w/ motor signs 1. simple
partial --> loss 1. simple partial
2. w/ somato- of --> generalized
sensory consciousness
symptoms 2. complex partial
2. w/ loss of --> generalized
3. w/ autonomic consciousness
symptoms at onset 3. simple partial
--> complex partial
4. w/ psychic --> generalized
symptoms
Simple partial seizures
with motor signs
 Focal motor w/o march
 Focal motor w/ march
 Versive
 Postural
 Phonatory
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
Simple partial seizures
with sensory symptoms
 Somato-sensory
 Visual
 Auditory
 Olfactory
 Gustatory
 Vertiginous
Simple partial seizures
with sensory symptoms
 Vertiginous symptoms
“Sudden sensation of
falling forward as in
empty space”
 No LOC
 Duration: 5 mins
Simple partial seizures
with autonomic symptoms
 Vomiting
 Pallor
 Flushing
 Sweating
 Pupil dilatation
 Piloerection
 Incontinence
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
Simple partial seizures
with psychic symptoms
 Dysphasia
 Dysmnesic
 Cognitive
 Affective
 Illusions
 Structured hallucinations
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
Complex Partial Seizures
 Simplepartial onset followed by
impaired consciousness
 with or without automatism
 With
impairment of consciousness at
onset
 with impairment of consciousness only
 with automatisms
Simple Partial Seizures
followed by Complex Partial
Seizures
 Seizure starts from
awake state
 Impairment of
consciousness
 Automatisms
 lip-smacking
 right leg
Complex Partial Seizures with
impairment of consciousness
at onset
 Suddenly sit up
 Roll about with
vehement
movement
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
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
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
Generalized seizures
 Absence
 Myoclonic
 Clonic
 Tonic
 Tonic-clonic
 Atonic
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

Absence seizures
 Stops
hyperventilating
 Mild eyelid clonus
 Slight loss of neck
muscle tone
 Oral automatisms
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)
Myoclonic seizures
 Symmetrical
myoclonic jerks
Clonic seizures
 Repetitive biphasic
jerky movements
 Repetitive vocalisation
synchronous with
clonic movements of
the chest (mechanical)
 Venous injection of
diazepam
 Passes urine
Tonic seizures
 Rigidviolent 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

Tonic seizures
 Elevates both hands
 Extreme forward
bending posture
 Keeps walking
without faling
 Passes urine
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
Tonic-clonic seizures
 Tonic stretching of
arms and legs
 Twitches in his face
and body
 Purses his lips and
growls
 Clonic phase
Atonic seizures
 Sudden reduction
in muscle tone
 Atonic head drop
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
Table 1. Modified ILAE Classification of Epilepsy Syndromes

Category Localization-related Generalized

Idiopathic Benign epilepsy of childhood with Benign myoclonic epilepsy in infancy

centrotemporal spikes Childhood absence epilepsy
(benign rolandic epilepsy) Juvenile absence epilepsy
Benign occipital epilepsy Juvenile myoclonic epilepsy

Symptomatic (of Temporal lobe Early myoclonic encephalopathy

underlying structural Frontal lobe Cortical dysgenesis
disease) Parietal lobe Metabolic abnormalities
Occipital lobe West syndrome
Lennox-Gastaut syndrome
Cryptogenic Any occurrence of partial seizures Epilepsy with myoclonic absences
without obvious pathology West syndrome (with unidentified
pathology)
Lennox-Gastaut syndrome (with
unidentified pathology)
Table 1. Modified ILAE Classification of Epilepsy Syndromes
(cond’)
Special syndromes Febrile convulsions
Seizures occurring only with toxic or metabolic
provoking factors
Neonatal seizures of any etiology
Acquired epileptic aphasia (Landau-Kleffner
syndrome)
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
 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
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
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 )

Diagnosis in epilepsy
 Aims:
 Differentiatebetween 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
Diagnosis in epilepsy
 Approach:
 History (from patient and witness)
 Physical examination

 Investigations
History
 Event
 Localization
 Temporal relationship
 Factors
 Nature
 Associated features
 Past medical history
 Developmental history
 Drug and immunization history
 Family history
 Social history
Physical Examination
 General
 esp. syndromal or non-syndromal
dysmorphic features, neurocutaneous
features
 Neurological
 Other system as indicated
 E.g. Febrile convulsion, infantile spasm
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)

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
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
International 10-20 System of Electrode
Placement in EEG
Electroencephalography (EEG)
 EEG interpretation in epilepsy
 Hemispheric or lobar asymmetries
 Periodic (regular, recurring)
 Background activity:
 Slow or fast
 Focal or generalized
 Paroxysmal activity:
 Epileptiform features – spikes, sharp waves
 Interictal or ictal
 Spontaneous or triggered
Electroencephalography (EEG)
 Certain epilepsy syndromes have characteristic or suggestive
features
 E.g.

Infantile spasms Hypsarrhythmia

Childhood absence epilepsy Generalized 3-Hz spike-wave

Juvenile myoclonic epilepsy Generalized/ multifocal 4-5 Hz spike-

wave and polyphasic-wave

Benign occipital epilepsy Unilateral/ bilateral occipital sharp/

sharp-slow activity that attenuates on
eye opening
Lennox-Gastaut syndrome Generalized/ bianterior spike-wave
activity at <2.5 Hz
 Electroencephalography (EEG)
 E.g. Brief absence seizure in an 18-year-old patient with
primary generalized epilepsy
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
Neuroimaging
 Structuralneuroimaging
 Functional neuroimaging
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
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)
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
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
Venn Diagram
 Seizure Therapy

Seizure

Specific Treatments General Treatment

Reassurance and
Anticonvulsant Surgery Education
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
Anticonvulsants
 Suppress repetitive action potentials in
epileptic foci in the brain
 Sodium channel blockade
 GABA-related targets

 Calcium channel blockade

 Others: neuronal membrane

hyperpolarisation
 Anticonvulsants

Drugs used in seizure disorders

Tonic-clonic and partial Absence seizures Myoclonic seizures Status Epilepticus Infantile Spasms

Cabamazepine Ethosuximide Valproic acid Short term Prolonged Corticotropin

Phenytoin Valproic acid control therapy Corticosteroids
Clonazepam
Valproic acid Clonazepam

Diazepam Phenytoin
Lorazepam Phenobarbital
Adverse Effects
 Teratogenicity
 Neural tube defects
 Fetal hydantoin syndrome

 Overdosage toxicity
 Life-threatening toxicity
 Hepatotoxicity

 Stevens-Johnson syndrome
 Abrupt withdrawal
Medical Intractability
 No known universal definition
 Risk factors
 High seizure frequency
 Early seizure onset

 Organic brain damage

 Established after adequate drug trials

 Operability
Surgery
 Curative
 Catastrophic unilateral or secondary
generalised epilepsies of infants and young
children
 Sturge-Weber syndrome
 Large unilateral developmental abnormalities

 Palliative
 Vagal nerve stimulation
Surgical Outcome
 Medical Intractability
 A well-localised epileptogenic zone
 EEG, MRI
 Low risk of new post-operative deficits
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.