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1. Seizures & Epilepsy
MBBS IV Group C
Tutor: Prof. V. Wong
16
th
Feb 2004

2. Outline
Definitions
Pathophysiology
Aetiology
Classification
Video demonstration
Diagnostic approach
Treatment
Quiz

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

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

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 SNis 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

15. Classification of seizures

16. Seizures
Partial
–Electrical discharges in a
relatively small group of
dysfunctional neurones in
onecerebral 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
consciousness
2. w/ loss of
consciousness
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
Versionof trunk
Postural
Left arm bent
Forcefully stretched fingers
Looks at watch
Note seizure

20. Simple partial seizures
with sensory symptoms
Somato-sensory
Visual
Auditory
Olfactory
Gustatory
Vertiginous

21. Simple partial seizures
with sensory symptoms
Vertiginous symptoms
“Sudden sensation of falling forward as in
empty space”
No LOC
Duration: 5 mins

22. Simple partial seizures
with autonomic symptoms
Vomiting
Pallor
Flushing
Sweating
Pupil dilatation
Piloerection
Incontinence

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

24. Simple partial seizures
with psychicsymptoms
Dysphasia
Dysmnesic
Cognitive
Affective
Illusions
Structured hallucinations

25. Simple partial seizure
with pyschic symptoms
Dysmnesic symptoms
“déjà-vu”
Affectivesymptoms
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

32. Generalized seizures
Absence
Myoclonic
Clonic
Tonic
Tonic-clonic
Atonic

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

34. Absence seizures
Stops
hyperventilating
Mild eyelid clonus
Slight loss of neck
muscle tone
Oral automatisms

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)

36. Myoclonic seizures
Symmetrical
myoclonic jerks

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

42. Atonic seizures
Sudden reduction
in muscle tone
Atonic head drop

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

57. International 10-20 System of Electrode
Placement in EEG

58. 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

59. 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

60. Electroencephalography (EEG)
E.g. Brief absence seizure in an 18-year-old patient with primary
generalized epilepsy

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

62. Neuroimaging
Structural neuroimaging
Functional neuroimaging

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

67. Venn Diagram

68. Seizure Therapy
Anticonvulsant Surgery
Specific Treatments
Reassurance and
Education
General Treatment
Seizure

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

72. Adverse Effects
Teratogenicity
Neural tube defects
Fetal hydantoin syndrome
Overdosage toxicity
Life-threatening toxicity
Hepatotoxicity
Stevens-Johnson syndrome
Abrupt withdrawal

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, 2
nd
edn. Butterworth
Heinemann.
6.Manford M, 2003, Practical Guide to Epilepsy,
Butterworth Heinemann.