Transcript Seizures & Epilepsy - University of Hong Kong

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
 Seizures
induced by somatic disorders
originating outside the brain

E.g. fever, infection, syncope, head trauma,
hypoxia, toxins, cardiac arrhythmias
Definition

Status epilepticus (SE)


Idiopathic SE


Continuous convulsion lasting longer than 30
minutes OR occurrence of serial convulsions
between which there is no return of consciousness
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


Idiopathic status epilepticus





Most common cause
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
 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
Pathophysiology
 Abnormal
area
 These
tissues — tumor, AVM, dead
regions of the brain may promote
development of novel hyperexcitable
synapses that can cause seizures
Pathophysiology
 Genetic
factors
 At
least 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 GABAmediated 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
relatively small group of
dysfunctional neurones in
one cerebral hemisphere
– Diffuse abnormal
electrical discharges
from both
hemispheres
– Aura may reflect site of
origin
– Symmetrically
involved
– + / - LOC
– No warning
– Always LOC
Partial Seizures
Simple
1. w/ motor
signs
2. w/ somatosensory
symptoms
3. w/ autonomic
symptoms
4. w/ psychic
symptoms
Complex
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
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
 Simple
partial 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 tonicclonic 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
 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

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
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
(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.
2.
Typical seizure affects mouth, face, +/- arm.
Speech arrest if dominant hemisphere,
consciousness often preserved, may generalize
especially when nocturnal, infrequent and easily
controlled
Onset is around 3-13 years old, good respond to
medication, always remits by mid-adolescence
Childhood absence epilepsy
1.
2.
3.
4.
5.
School age ( 4-10 years ) with a peak age of onset at 6-7
years
Brief seizures, lasting between 4 and 20 seconds
3Hz Spike and wave complexes is the typical EEG
abnormality
Sudden onset and interruption of ongoing activity, often with a
blank stare.
Precipitated by a number of factors i.e. fear, embarrassment,
anger and surprise. Hyperventilation will also bring on attacks.
Juvenile myoclonic seizure
1.
2.
3.
Around time of puberty
Myoclonic ( sudden spasm of muscles ) jerks → generalized
tonic clonic seizure without loss of consciousness
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:
 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
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
 E.g.
system as indicated
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 spikewave 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
seizure
in the light of proximity to
Neuroimaging
 Structural
neuroimaging
 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
 When
in diagnosis of epilepsy:
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
Anticonvulsant
Surgery
General Treatment
Reassurance and
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
Cabamazepine
Phenytoin
Valproic acid
Absence seizures
Ethosuximide
Valproic acid
Clonazepam
Myoclonic seizures
Valproic acid
Clonazepam
Status Epilepticus
Short term
control
Diazepam
Lorazepam
Infantile Spasms
Prolonged
therapy
Phenytoin
Phenobarbital
Corticotropin
Corticosteroids
Adverse Effects
 Teratogenicity
 Neural
tube defects
 Fetal hydantoin syndrome
 Overdosage
toxicity
 Life-threatening toxicity
 Hepatotoxicity
 Stevens-Johnson
 Abrupt
withdrawal
syndrome
Medical Intractability
 No
known universal definition
 Risk factors
 High
seizure frequency
 Early seizure onset
 Organic brain damage
 Established
 Operability
after adequate drug trials
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,
 Low
MRI
risk of new post-operative deficits
References
1.
2.
3.
4.
5.
6.
Stedman’s Medical Dictionary.
MDConsult: Nelson’s textbook.
Illustrated Textbook of Pediatrics.
Video atlas of epileptic seizures – Classical
examples, International League against
epilepsy.
Guberman AH, Bruni J, 1999, Essentials of
Clinical Epilepsy, 2nd edn. Butterworth
Heinemann.
Manford M, 2003, Practical Guide to
Epilepsy, Butterworth Heinemann.