Transcript 14-epilepsy - WordPress.com

Prof Mohammad Salah Abduljabbar
 Incidence:
Approximately 45/100,000 per year
 Prevalence:
0.5-1% (2.5 million with epilepsy)
- 14 years or younger
13%
- 15 to 64 years
63%
- 65 years and older
24%
 Cumulative risk of epilepsy: 1.3% - 3.1%
 Epilepsy refractory to AEDs: 20-30%
2


A chronic neurologic disorder manifesting by
repeated epileptic seizures (attacks or fits)
which result from paroxysmal uncontrolled
discharges of neurons within the central
nervous system (gray matter disease).
The clinical manifestations range from a major
motor convulsion to a brief period of lack of
awareness. The stereotyped and uncontrollable
nature of the attacks is characteristic of
epilepsy.
 Seizure
(Convulsion)
Clinical manifestation of synchronized
electrical discharges of neurons
 Epilepsy
Present when 2 or more unprovoked
seizures occur at an interval greater
than 24 hours apart
 Provoked
seizures
Seizures induced by somatic disorders
originating outside the brain
(E.g. fever, infection, syncope, head
trauma, hypoxia, toxins, cardiac
arrhythmias)

Status epilepticus (SE):
Continuous convulsion lasting longer than 30
minutes OR occurrence of serial convulsions
between which there is no return of
consciousness

Idiopathic seizure:
Seizure develops in the absence of an
underlying CNS lesion/insult

Symptomatic seizure:
Seizure occurs as a result of an underlying
neurological disorder or a metabolic
abnormality

Epileptic
- Idiopathic
(70-80%)
- Cerebral tumour
- Neurodegenerative disorders
- Neurocutaneous syndromes
- Secondary to
 Cerebral damage: e.g. congenital
infections, HIE, interventricular
haemorrhage
 Cerebral dysgenesis/malformation: e.g.
hydrocephalus

Non-epileptic
 Febrile convulsions
 Metabolic
- Hypoglycaemia, Hypocalcaemia,
- Hypomagnesaemia, Hypernatremia
and Hyponatremia
 Head trauma
 Meningitis
 Encephalitis
 Poisons/toxins


Idiopathic status epilepticus
◦ Non-compliance to anticonvulsants
◦ Sudden withdrawal of anticonvulsants
◦ Sleep deprivation
◦ Inter current infection
Symptomatic status epilepticus
◦ Anoxic encephalopathy
◦ Encephalitis, meningitis
◦ Congenital malformations of the brain
◦ Electrolyte disturbances, drug/lead intoxication,
extreme hyperpyrexia, brain tumour


The 19th century neurologist Hughlings
Jackson suggested “a sudden excessive
disorderly discharge of cerebral neurons“ as
the causation of epileptic seizures.
Recent studies in animal models of focal
epilepsy suggest a central role for the
excitatory neurotransmiter glutamate
(increased) and inhibitory gamma amino
butyric acid (GABA) (decreased)


Still unknown
Some proposals:
◦ Excitatory glutamatergic synapses
◦ Excitatory amino acid neurotransmitter
(glutamate, aspartate)
◦ Abnormal tissues — tumour, AVM, dead area
◦ Genetic factors
◦ Role of substantia nigra and GABA


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

Abnormal tissues — tumour, AVM, dead
area
These regions of the brain may promote
development of novel hyperexcitable
synapses that can cause seizures

Genetic factors
◦ At least 20 %
◦ Some examples
 Benign neonatal convulsions.
 Juvenile myoclonic epilepsy.
 Progressive myoclonic epilepsy.
16


The modern classification of the
epilepsies is based upon the nature of
the seizures rather than the presence or
absence of an underlying cause.
Seizures which begin focally from a
single location within one hemisphere
are thus distinguished from those of a
generalised nature which probably
commence in a deeper structures
(brainstem? thalami) and project to both
hemispheres simultaneously.
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
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
consciousn
ess
2. w/ loss
of
consciousn
ess at onset
Secondary
generalized
1. simple partial
--> generalized
2. complex
partial
--> generalized
3. simple partial
--> complex
partial
--> generalized

Simple partial seizures
Motor, sensory, vegetative or psychic
symptoms Typically consciousness is preserved
Right temporal
seizure with
maximal phase
reversal in the
right temporal
lobe
21
- Focal motor without march
- Focal motor with march





Sudden onset
from sleep
Version of trunk
Postural
◦ Left arm bent
◦ Forcefully
stretched fingers
Looks at watch
Note seizure
 Visual
 Auditory
 Olfactory
 Gustatory
 Vertiginous



Vertiginous
symptoms
“Sudden sensation
of falling forward
as in empty space”
No LOC
Duration: 5 mins







Vomiting
Pallor
Flushing
Sweating
Pupil dilatation
Piloerection
Incontinence





Stiffness in Left
cheek
Difficulty in
articulating
Right side of mouth
is dry
Salivating on the Left
side
Progresses to tongue
and back of throat
Dysphasia
 Dysmnesic
 Cognitive
 Affective
 Illusions
 Structured hallucinations





Dysmnesic
symptoms
◦ “déjà-vu”
Affective symptoms
◦ fear and panic
Cognitive
Structured
hallucination
◦ living through a
scene of her
former life again
Simple partial onset followed by
impaired consciousness
◦ with or without automatism
 With impairment of consciousness at
onset
◦ with impairment of consciousness
only
◦ with automatisms

Seizure starts from awake
state
 Impairment of consciousness
 Automatisms
◦ lip-smacking
◦ right leg

 Suddenly
sit up
 Roll about with
vehement movement
Simple Partial Seizures to
Generalized Seizures
 Complex Partial Seizures to
Generalized Seizures
 Simple Partial Seizures to Complex
Partial Seizures to Generalized
Seizures







Turns to his right with upper body
and bends his left arm
Stretches body
LOC
Tonic-clonic seizure
Relaxation phase
Postictal sleep




Initially unable to communicate but
understands
Automatism
◦ Smacking
◦ Hand-rubbing
Abolished communication
Generalized tonic-clonic seizure
Absence
 Myoclonic
 Clonic
 Tonic
 Tonic-clonic
 Atonic

Absences
 Myoclonic seizures
 Clonic seizures
 Tonic seizures
 Atonic seizures

◦ Sudden onset
◦ Interruption of ongoing activities
◦ Blank stare
◦ Brief upward rotation of eyes
◦ Few seconds to 1/2 minute
◦ Evaporates as rapidly as it started




Stops
hyperventilating
Mild eyelid clonus
Slight loss of neck
muscle tone
Oral automatisms
◦ Sudden, brief, shock-like
◦ Predominantly around the hours of
going to or awakening from sleep
◦ May be exacerbated by volitional
movement (action myoclonus)
◦ Symmetrical myoclonic jerks
◦ Repetitive biphasic jerky
movements
◦ Repetitive vocalisation
synchronous with clonic
movements of the chest
(mechanical)
◦ Passes urine
◦ 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
Elevates both hands
 Extreme forward bending
posture
 Keeps walking without
falling
 Passes urine

◦
◦
◦
◦
◦
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 stretching of arms
and legs
 Twitches in his face and
body
 Purses his lips and growls
 Clonic phase

◦ Sudden reduction in
muscle tone
◦ Atonic head drop



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.
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.
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 )

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
The following should be considered in the diff. dg. of epilepsy:
 Syncope attacks (when pt. is standing; results from global
reduction of cerebral blood flow; prodromal pallor, nausea,
sweating; jerks!)
 Cardiac arrythmias (e.g. Adams-Stokes attacks). Prolonged
arrest of cardiac rate will progressively lead to loss of
consciousness – jerks!
 Migraine (the slow evolution of focal hemisensory or
hemimotor ssymptoms in complicated migraine contrasts
with more rapid “spread“ of such manifestation in SPS.
Basilar migraine may lead to loss of consciousness!
 Hypoglycemia – seizures or intermittent behavioral
disturbances may occur.
 Narcolepsy – inappropriate sudden sleep episodes
 Panic attacks
 PSEUDOSEIZURES – psychosomatic and personality disorders
Approach
◦History (from patient and witness)
◦Physical examination
◦Investigations






Event
◦ Localization
◦ Temporal relationship
◦ Factors
◦ Nature
◦ Associated features
Past medical history
Developmental history
Drug and immunization history
Family history
Social history
 General
◦ esp. syndrome or non-syndromal
dysmorphic features,
neurocutaneous features
 Neurological
 Other system as indicated
◦ E.g. Febrile convulsion, infantile
spasm




The concern of the clinician is that epilepsy may be
symptomatic of a treatable cerebral lesion.
Routine investigation: Haematology, biochemistry
(electrolytes, urea and calcium), chest X-ray,
electroencephalogram (EEG).
Neuroimaging (CT/MRI) should be performed in all persons
aged 25 or more presenting with first seizure and in those
pts. with focal epilepsy irrespective of age.
Specialised neurophysiological investigations: Sleep deprived
EEG, video-EEG monitoring.
Advanced investigations (in pts. with intractable focal
epilepsy where surgery is considered): Neuropsychology,
Semiinvasive or invasive EEG recordings, MR Spectroscopy,
Positron emission tomography (PET) and ictal Single photon
emission computed tomography (SPECT)

I. Exclusion of differentials:
◦ Bedside: urinalysis
◦ Hematological: CBP
◦ Biochemical: U&Es, Calcium, glucose, ABGs
◦ Radiological: CXR, CT head
◦ Toxicological: screen
◦ Microbiological: LP
(Always used with justification)

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
 EEG
indicated whenever epilepsy
suspected
 Uses of EEG in epilepsy
◦ Diagnostic: support diagnosis, classify
seizure, localize focus, quantify
◦ Prognostic: adjust anti-epileptic
treatment

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
◦ Normal in 10-20% of epileptic patients
◦ Background slowed by:
 AED, diffuse cerebral process, postictal
state
◦ Artifact from:
 Eye rolling, tremor, other movement,
electrodes
 Structural
neuroimaging
 Functional
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
 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)
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

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
Seizure Therapy
Seizure
Specific Treatments
Anticonvulsant
Surgery
General Treatment
Reassurance and
Education




Information leaflets and information
about support group
Avoidance of hazardous physical
activities
Management of prolonged fits
◦ Recovery position
◦ Rectal diazepam
Side effects of anticonvulsants



The majority of pts respond to drug therapy
(anticonvulsants). In intractable cases surgery may
be necessary. The treatment target is seizurefreedom and improvement in quality of life!
The commonest drugs used in clinical practice are:
Carbamazepine, Sodium valproate, Lamotrigine
(first line drugs) Levetiracetam, Topiramate,
Pregabaline (second line drugs) Zonisamide,
Eslicarbazepine, Retigabine (new AEDs)
Basic rules for drug treatment: Drug treatment
should be simple, preferably using one
anticonvulsant (monotherapy). “Start low, increase
slow“. Add-on therapy is necessary in some patient


If patient is seizure-free for three years,
withdrawal of pharmacotherapy should be
considered. Withdrawal should be carried out only
if patient is satisfied that a further attack would
not ruin employment etc. (e.g. driving license). It
should be performed very carefully and slowly!
20% of pts will suffer a further sz within 2 yrs.
The risk of teratogenicity is well known (~5%),
especially with valproates, but withdrawing drug
therapy in pregnancy is more risky than
continuation. Epileptic females must be aware of
this problem and thorough family planning
should be recommended. Over 90% of pregnant
women with epilepsy will deliver a normal child.

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
Teratogenicity
◦ Neural tube defects
◦ Fetal hydantoin syndrome
 Over dosage toxicity
 Life-threatening toxicity
◦ Hepatotoxicity
◦ Stevens-Johnson syndrome
 Abrupt withdrawal

No known universal definition
 Risk factors
◦ High seizure frequency
◦ Early seizure onset
◦ Organic brain damage
 Established after adequate drug trials
 Operability

 Curative
◦ Catastrophic unilateral or secondary
generalised epilepsies of infants and young
children
 Sturge-Weber syndrome
 Large unilateral developmental
abnormalities
 Palliative
◦ Vagal nerve stimulation




A proportion of the pts with intractable epilepsy
will benefit from surgery.
Epilepsy surgery procedures: Curative (removal of
epileptic focus) and palliative (seizure-related risk
decrease and improvement of the QOL)
Curative (resective) procedures: Anteromesial
temporal resection, selective
amygdalohippocampectomy, extensive
lesionectomy, cortical resection, hemispherectomy.
Palliative procedures: Corpus callosotomy and
Vagal nerve stimulation (VNS).


Medical Intractability
A well-localised epileptogenic zone
In EEG, MRI

Low risk of new post-operative deficits
A condition when consciousness does not
return between seizures for more than 30 min.
This state may be life-threatening with the
development of pyrexia, deepening coma and
circullatory collapse. Death occurs in 5-10%.
 Status epilepticus may occur with frontal lobe
lesions (incl. strokes), following head injury, on
reducing drug therapy, with alcohol withdrawal,
drug intoxication, metabolic disturbances or
pregnancy.
 Treatment: AEDs intravenously ASAP, event.
general anesthesia with propofol or thipentone
should be commenced immediately.

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.