Transcript Generalized seizures

Epilepsy
Definitions
A seizure is an abnormal, unregulated
electrical discharge that occurs within the
brain's cortical gray matter and transiently
interrupts normal brain function. A seizure
typically causes altered awareness,
abnormal sensations, focal involuntary
movements, or convulsions (widespread
violent involuntary contraction of voluntary
muscles).
About 2% of adults have a seizure at some
time during their life.
Two thirds of these people never have
another one.
Epilepsy (also called epileptic
seizure disorder)
a chronic brain disorder characterized by
recurrent (≥ 2), unprovoked seizures (ie,
not related to reversible stressors). A single
seizure is not considered an epileptic
seizure. Epilepsy is often idiopathic, but
various brain disorders, such as
malformations, strokes, and tumors, can
cause symptomatic epilepsy.
Symptomatic epilepsy
epilepsy due to a known cause (eg, brain
tumor, stroke). The seizures it causes are
called symptomatic epileptic seizures. Such
seizures are most common among neonates
and the elderly.
Nonepileptic seizures
are provoked by a temporary disorder or
stressor (eg, metabolic disorders, CNS
infections, cardiovascular disorders, drug
toxicity or withdrawal, psychogenic
disorders). In children, fever can provoke a
seizure
Psychogenic nonepileptic seizures
(pseudoseizures)
symptoms that simulate seizures in patients
with psychiatric disorders but that do not
involve an abnormal electrical discharge in
the brain.
Etiology
Seizures can result from either primary central
nervous system dysfunction or an underlying
metabolic derangement or systemic disease.
This distinction is critical,
since therapy must be directed at the underlying
disorder as well as at seizure control.
The age of the patient may help in establishing the
cause of seizures .
AGE OF ONSET ;PROBABLE CAUSE
Neonatal Congenital maldevelopment,
birthinjury, anoxia, metabolic disorders
hypocalcemia, hypoglycemia,vitamin B6
deficiency, biotinidase deficiency,
phenylketonuria, and others)
Infancy (1–6 months) As above; infantile
spasms; West syndrome
Early childhood (6 months–3 years)
Infantile spasms, febrile
convulsions,birth injury and anoxia,
infections,trauma, metabolic disorders,
cortical dysgenesis, accidental drug
poisoning
Childhood (3–10 years ) Perinatal
anoxia, injury at birth or
later,infections, thrombosis of cerebral
arteries or veins, metabolic
disorders,cortical malformations,
LennoxGastaut syndrome, “idiopathic,”probably
inherited, epilepsy (Rolandic epilepsy)
Adolescence (10–18 years ) Idiopathic
epilepsy, including
genetically transmitted types, juvenile
myoclonic epilepsy, trauma, drugs
Early adulthood 18-25 years ) Idiopathic
epilepsy, trauma, neoplasm,
withdrawal from alcohol or other
sedative drugs
Middle age (35–60 years ) Trauma,
neoplasm, vascular disease,
alcohol or other drug withdrawal
Late life (over 60 years ) Vascular
disease (usually
postinfarction), tumor, abscess,
degenerative disease, trauma
Etiology and age of onset
Classification
Generalized
In generalized seizures, the aberrant electrical
discharge diffusely involves the entire
cortex of both hemispheres from the onset,
and consciousness is usually lost.
Generalized seizures result most often from
metabolic disorders and sometimes from
genetic disorders.
Classification
Infantile spasms
Absence seizures
Tonic-clonic seizures
Tonic seizures
Atonic seizures
Myoclonic seizures (eg, in juvenile myoclonic
epilepsy)
Classification
Partial seizures
In partial seizures, the excess neuronal
discharge occurs in one cerebral cortex, and
most often results from structural
abnormalities.
Classification
Simple (no impairment of consciousness)
Complex (reduced but not complete loss of
consciousness)
Classification
Partial seizures may evolve into a generalized
seizure (called secondary generalization),
which causes loss of consciousness.
Secondary generalization occurs when a
partial seizure spreads and activates the
entire cerebrum bilaterally. Activation may
occur so rapidly that the initial partial
seizure is not clinically apparent or is very
brief.
Symptoms and Signs
Seizures may be preceded by an aura. Auras are
simple partial seizures that begin focally. Auras
may consist of motor activity or sensory,
autonomic, or psychic sensations (eg, paresthesias,
a rising epigastric sensation, abnormal smells, a
sensation of fear, a déjà vu or jamais vu
sensation). In jamais vu, a familiar place or
experience feels very unfamiliar—the opposite of
déjà vu.
Most seizures end spontaneously in 1 to 2
min. Generalized seizures are often
followed by a postictal state, characterized
by deep sleep, headache, confusion, and
muscle soreness; this state lasts from
minutes to hours. Sometimes the postictal
state includes Todd paralysis (a transient
neurologic deficit, usually weakness, of the
limb contralateral to the seizure focus).
Most patients appear neurologically normal between
seizures, although high doses of the drugs used to
treat seizure disorders, particularly
anticonvulsants, can reduce alertness.
Any progressive mental deterioration is usually
related to the neurologic disorder that caused the
seizures rather than to the seizures themselves.
Rarely, seizures are unremitting, as in status
epilepticus.
Partial seizures
Simple partial seizures cause motor, sensory, or
psychomotor symptoms without loss of
consciousness. Specific symptoms reflect the
affected area of the brain .
In jacksonian seizures, focal motor symptoms begin
in one hand, then march up the arm.
Other focal seizures affect the face first, then spread
to an arm and sometimes a leg. Some partial motor
seizures begin with an arm raising and the head
turning toward the raised arm
Complex partial seizures are often preceded
by an aura. During the seizure, patients may
stare. Consciousness is impaired, but
patients have some awareness of the
environment (eg, they purposefully
withdraw from noxious stimuli).
Oral automatisms (involuntary chewing or lip smacking)
Limb automatisms (eg, automatic purposeless movements of
the hands)
Utterance of unintelligible sounds without understanding
what they say
Resistance to assistance
Tonic or dystonic posturing of the extremity contralateral to
the seizure focus
Head and eye deviation, usually in a direction contralateral to
the seizure focus
Motor symptoms subside after 1 to 2 min, but
confusion and disorientation may continue
for another 1 or 2 min. Postictal amnesia is
common.
Generalized seizures:
Consciousness is usually lost, and motor
function is abnormal from the onset.
Tonic-clonic seizures
may be primary or secondarily generalized. Primarily
generalized seizures typically begin with an outcry; they
continue with loss of consciousness and falling, followed
by tonic contraction, then clonic (rapidly alternating
contraction and relaxation) motion of muscles of the
extremities, trunk, and head. Urinary and fecal
incontinence, tongue biting, and frothing at the mouth
sometimes occur. Seizures usually last 1 to 2 min. There is
no aura. Secondarily generalized tonic-clonic seizures
begin with a simple partial or complex partial seizure.
Typical absence seizures
consist of 10- to 30-sec loss of consciousness
with eyelid fluttering. Patients do not fall or
convulse; they abruptly stop activity, then
just as abruptly resume it, with no postictal
symptoms or knowledge that a seizure has
occurred. Absence seizures are genetic and
occur predominantly in children.
Typical absence seizures
Without treatment, such seizures are likely to
occur many times a day. Seizures often
occur when patients are sitting quietly, can
be precipitated by hyperventilation, and
rarely occur during exercise. Neurologic
and cognitive examination results are
usually normal.
Atonic seizures
occur most often in children, usually as part of
Lennox-Gastaut syndrome. Atonic seizures
are characterized by brief, complete loss of
muscle tone and consciousness. Children
fall or pitch to the ground, risking trauma,
particularly head injury.
Tonic seizures
occur most often during sleep, usually in
children. The cause is usually the LennoxGastaut syndrome. Tonic (sustained)
contraction of axial muscles may begin
abruptly or gradually, then spread to the
proximal muscles of the limbs. Tonic
seizures usually last 10 to 15 sec. In longer
tonic seizures, a few, rapid clonic jerks may
occur as the tonic phase ends.
Myoclonic seizures
brief, lightning-like jerks of a limb, several
limbs, or the trunk. They may be repetitive,
leading to a tonic-clonic seizure. The jerks
may be bilateral or unilateral. Unlike other
seizures with bilateral motor movements,
consciousness is not lost unless the
myoclonic seizure progresses into a
generalized tonic-clonic seizure.
History
Patients should be asked about unusual
sensations, suggesting an aura and thus a
seizure, and about typical seizure
manifestations. Patients typically do not
remember generalized seizures, so a
description of the seizure itself must be
obtained from witnesses.
History should include information about the
first and any subsequent seizures (eg,
duration, frequency, sequential evolution,
longest and shortest interval between
seizures, aura, postictal state, precipitating
factors).
All patients should be asked about
risk factors for seizures:
Prior head trauma or CNS infection
Known neurologic disorders
Drug use or withdrawal, particularly of
recreational drugs
Alcohol withdrawal
Nonadherence to anticonvulsants
Family history of seizures or neurologic
disorders
Patients should also be asked about rare
triggers (eg, repetitive sounds, flashing
lights, video games, touching certain parts
of the body) and about sleep deprivation,
which can lower the seizure threshold.
Physical examination
In patients who have lost consciousness, a
bitten tongue, incontinence (eg, urine or
feces in clothing), or prolonged confusion
after loss of consciousness suggest seizure.
pseudoseizures can usually be
distinguished from true seizures by
clinical characteristics:
Pseudoseizures often last longer (several minutes or more).
Postictal confusion tends to be absent.
Typical tonic phase activity, followed by clonic phase, usually
does not occur.
The progression of muscular activity does not correspond to
true seizure patterns (eg, jerks moving from one side to the
other and back [nonphysiologic progression]), exaggerated
pelvic thrusting).
Intensity may wax and wane.
Vital signs, including temperature, usually remain normal.
Patients often actively resist passive eye opening.
Physical examination rarely indicates the
cause when seizures are idiopathic but may
provide clues when seizures are
symptomatic
Clinical Clues to the Causes of Symptomatic Seizures
Finding
Possible Cause
Fever and stiff neck
Meningitis
Subarachnoid hemorrhage
Meningoencephalitis
Papilledema
Increased intracranial pressure
Loss of spontaneous venous pulsations (noted
during funduscopy)
Increased intracranial pressure ( specificity is 80–
90%*)
Generalized neuromuscular irritability (eg,
tremulousness, hyperreflexia)
Generalized neuromuscular irritability (eg,
tremulousness, hyperreflexia)Drug toxicity (eg,
sympathomimetics)Withdrawal syndromes (eg, of
alcohol or sedatives)Certain metabolic disorders
(eg, hypocalcemia, hypomagnesemia)
Focal neurologic defects (eg, asymmetry of reflexes
or muscle strength)
Structural abnormality (eg, tumor, stroke)
Postictal paralysis
Skin lesions (eg, axillary freckling or café-au-lait
spots, hypomelanotic skin macules, shagreen
patches)
Neurocutaneous disorders (eg, neurofibromatosis,
tuberous sclerosis
EEG
EEG is critical in the diagnosis of epileptic seizures,
particularly of complex partial or absence status
epilepticus, when EEG may be the most definitive
indication of a seizure.
EEG may detect epileptiform abnormalities (spikes,
sharp waves, spike and slow-wave complexes,
polyspike and slow-wave complexes).
Epileptiform abnormalities may be bilateral,
symmetric, and synchronous in patients with
primary generalized seizures and may be localized
in patients with partial seizures.
However, normal EEG cannot exclude the diagnosis
of epileptic seizures, which must be made
clinically. EEG is less likely to detect
abnormalities if seizures are infrequent. The initial
EEG may detect an epileptiform abnormality in
only 30 to 55% of patients with a known epileptic
seizure disorder. Serial EEG may detect
epileptiform abnormalities in up to 80 to 90% of
such patients.
Primary generalized epilepsy
After a first seizure, cerebral imaging with CT
or MRI is advisable, particularly in patients
over 20 years of age, although the yield of
structural lesions is low unless there are
focal features to the seizure or there are
focal signs.
Indications for imaging
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Epilepsy starts after the age of 20 years
Seizures have focal features clinically
EEG shows a focal seizure source
Control of seizures is difficult or
deteriorates
Investigations
Epileptic nature of attacks?
Ambulatory EEG
Videotelemetry
Type of epilepsy?
Standard EEG
Sleep EEG
EEG with special electrodes (foramen ovale, subdural (
Structural lesion?
CT
MRI
Metabolic disorder?
Urea and electrolytes
Liver function tests
Blood glucose
Serum calcium, magnesium
Inflammatory or infective disorder?
Full blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP )
Chest X-ray
Serology for syphilis, HIV, collagen disease
CSF examination
Prognosis
With treatment, seizures are eliminated in one third
of patients with epileptic seizures, and frequency
of seizures is reduced by > 50% in another third.
About 60% of patients whose seizures are wellcontrolled by drugs can eventually stop the drugs
and remain seizure-free.
Sudden unexplained death in epilepsy (SUDEP) is a
rare complication of unknown cause.
Treatment
Elimination of the cause if possible
Avoidance of or precautions during situations
when loss of consciousness could be life
threatening
Drugs to control seizures
Surgery if ≥ 2 drugs in therapeutic doses do
not control seizures
During a generalized tonic-clonic seizure, injury
should be prevented by loosening clothing around
the neck and placing a pillow under the head.
Attempting to protect the tongue is futile and
likely to damage the patient's teeth or the rescuer's
fingers. Patients should be rolled onto their left
side to prevent aspiration. These measures should
be taught to the patient's family members and
coworkers.
Because partial seizures can become
generalized, patients are at risk of losing
consciousness and thus should be advised to
take certain precautions. Until seizures are
controlled, patients should refrain from
activities in which loss of consciousness
could be life threatening (eg, driving,
swimming, climbing, operating power tools,
bathing in a bathtub).
Anticonvulsant therapy
Drug treatment should certainly be considered after more than
one seizure has occurred and the patient agrees that seizure
control is worthwhile; A wide range of anti-epilepsy drugs
is available.
The mode of action of these drugs is either to increase
inhibitory neurotransmission in the brain or to alter
neuronal sodium channels in a way to prevent abnormally
rapid transmission of impulses.
In 80 % ofpatients whose epilepsy is controlled,only a single
drug is necessary.
The combination of more than 2 drugs is seldom required.
Dose regimens should be kept as simple as possible to
promote compliance.
Anticonvulsant therapy
• With few exceptions, There is no hard evidence indicating
that one drug is superior to another.
• The first choice should be one of the first line drug with
the more recently introduced drugs as second choice.
• Phenytoin and carbamazepine are not ideal for a young
woman wishing to use oral contraceptives (inducer drugs).
• Carbamazepine, lamotrigene and sodium valproate are
preferable to phenytoin because of the side effect profile of
the latter and its complicated pharmacokinetics.
Guidelines for choice of AEDs
Epilepsy type
First-line drug
Second line
Partial and/or
secondary GTCS
carbamazepine
Lamotrigine
Sodium
valproate
Levetiracetam
topiramate
Primary GTCS
Sodium
valproate
Lamotrigine
topiramate
absence
ethosuximide
Sodium
valproate
myoclonic
Sodium
valproate
clonazepam
Third line
Guidelines for anticonvulsant therapy
• Start with one first-line drug.
• Start at a low dose , increase,dose until effective control of
seizures is achieved or side effects develop (drug level may
be helpful).
• Optimise compliance (use minimum number of doses per
day ).
• If first drug fails,start second first-line drug while
gradually withdrawing first.
• If second drug fails,start second-line drug in combination
of preferred first-line drug at maximum tolerated dose
(beware of interaction )
Guidelines for anticonvulsant therapy
• If this combination fails replace second-line drug
with alternative second-line drug.
• If this combination fails, check compliance and
reconsider diagnosis (is there an occult structural
or metabolic lesion or are seizures truly epileptic
?).
• If this combination fails consider alternative nonpharmacological treatment (surgery or VNS).
• Do not use more than 2 drugs in combination at
any one time.
Monitoring therapy
With some drugs such as phenytoin and carbamazepine ,
occasional measurement of the blood level can be a guide
whether the patient is on an appropriate dose and is
complying with the medication ,but blood levels need to be
interpreted carefully.
The dose of AED in an individual patient should primarily be
governed by the efficacy of seizure control and the
development of side effects rather than blood levels alone.
With sodium valproate, there is a poor relationship between
blod level and anticonvulsant efficacy and so levels are
only useful to assess compliance.
Repeated measurement of blood levels is not generally useful
and monitoring is of most value in dealing with suspected
toxicity,the pharmacokinetic effect of pregnancy or in
suspected non-compliance.
Withdrawing AEDs
After complete control of seizures for 2 – 4
years,withdrawal of medication may be
considered.
Childhood – onset epilepsy particularly classical
absence seizures carries the best prognosis.
Juvenile myoclonic epilepsy have a marked liability
to recur after drug withdrawal.
Seizures that begin in adult life particularly those
with partial features are likely to recur especially
if there is a structural lesion.
Withdrawing AEDs
Overall ,the overall recurrence rate is about 40
%.
The EEG is generally a poor predictor of
recurrence but if the record is still very
abnormal,drug withdrawal is unwise.
Withdrawal should be undertaken slowly ,
reducing the drug dose gradually over 6-12
months.
VNS THERAPY
Vagus Nerve Stimulation
• VNS Therapy consists of electrical signals
• that are applied to the vagus nerve in the
• neck for transmission to the brain.
 The vagus nerve has proven to be a good
 way to communicate with the brain
 because:
There are few if any pain fibers in the vagus nerve.
Over 80% of the electrical signals applied to the vagus
 nerve in the neck are sent upwards to the brain.
•
The surgical procedure to attach the lead to the vagus
• nerve does not involve the brain. It is not brain surgery.
•

THE KETOGENIC DIET
 Very high in fat and low in carbohydrates and
protein.
 4 grams of fat for each gram of protein and
carbohydrate consumed.
 Caloric intake is usually 75% of the recommended
calorie intake
 A minimum of 1 gram of protein per kilogram of
body weight per day is provided.
 Restricting fluid to 65 mL per kilogram of body
weight per day
Pregnancy
With the exception of gabapentine, all AEDs is
associated with fetal abnormalities such as cleft lip
,spina bifida and cardiac defects.
The risk is greatest when treatment is given in the 1st
trimester ,rising from a background risk of 2-4%
to about 4-8% with one drug and to 15 % with two
drugs or more.
Folic acid (5 mg daily ) taken 2 months before
conception may reduce the risk of some fetal
abnormalities
Pregnancy
Seizures often become more frequent during
pregnancy , especially during the 3rd trimester
when plasma anticonvulsant level tend to fall.
Monitoring of blood levels of anticonvulsants can be
helpful with adjustment of drug doses.
Occasionally in a well controlled patient , AEDs can
be withdrawn before conception ,but if major
seizures have occurred in the preceding year , this
is unwise , since uncontrolled maternal seizures
represent a significant risk to the fetus .
Contraception
Many AEDs, including carbamazepine,phenytoin,barbiturate ,
induce hepatic enzymes,accelerate metabolism of estrogen
and cause breakthrough bleeding and contraceptive failure.
Lamotrigine and oxcarbazepine have little interaction.
Sodium valproate has no interaction with oral contraceptives.
The safest policy is to use an alternative contraceptive
method, but it is sometimes possible to overcome the
problem by giving higher dose of estrogen.
Status epilepticus
Defined a seizure or a series of seizures lasting 30 minutes without the
patient regaining awareness between attacks . Most commonly, this
refers to recurrent tonic clonic seizures (major status) and is a lifethreatening medical emergency. Partial motor status is obvious
clinically, but complex partial status and absence status may be
difficult to diagnose because the patient may merely present in a
dazed, confused state. Status is never the presenting feature of
idiopathic epilepsy but may be precipitated by abrupt withdrawal of
anticonvulsant drugs, the presence of a major structural lesion or acute
metabolic disturbance, and tends to be more common with frontal
epileptic foci .It should be remembered that psychogenic or nonepileptic attacks commonly masquerade as 'status epilepticus', so
electrophysiological confirmation of the seizures should be obtained as
early as possible
Management of status epilepticus
Initial :
Ensure airway is patent , give oxygen to prevent cerebral
hypoxia and secure intravenous access.
Draw blood for glucose , urea and electrolytes (including Ca
and Mg), and liver function and store a sample for future
analysis (e.g. drug misuse ).
Give diazepam 10 mg i.v. or rectally or lorazepam 4 mg i.v. –
repeat once only after 15 minutes.
Transfer to intensive care area ,monitor neurological
condition,blood pressure ,respiration and blood
gases.intubating and ventilating patient if appropriate.
Management of status epilepticus
If seizure continue after 30 minutes
Intravenous infusion (with cardiac monitoring) with one
of:
Phenytoin: i.v. infusion of 15 mg/kg at 50 mg/min
Fosphenytoin: i.v. infusion of 15 mg/kg at 100 mg/min
Phenobarbital: i.v. infusion of 10 mg/kg at 100 mg/min
If seizures still continue after 30-60 mins
Start treatment for refractory status with intubation and
ventilation, and general anaesthesia using propofol or
thiopental
Management of status epilepticus
Once status controlled
Commence longer-term anticonvulsant medication
with one of :
Sodium valproate 10 mg/kg i.v. over 3-5 mins, then 8002000 mg/day
Phenytoin: give loading dose (if not already used as
above) of 15 mg/kg, infuse at < 50 mg/min, then 300
mg/day
Carbamazepine 400 mg by nasogastric tube, then 4001200 mg/day
Investigate cause
Differential Diagnosis of Seizures
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Syncope
Vasovagal syncope
Cardiac arrhythmia
Valvular heart disease
Cardiac failure
Orthostatic hypotension
Psychological disorders
Psychogenic seizure
Hyperventilation
Panic attack
Metabolic disturbances
Alcoholic blackouts
Delirium tremens
Hypoglycemia
Hypoxia
Psychoactive drugs (e.g.,
hallucinogens)
Migraine
Confusional migraine
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Basilar migraine
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Transient ischemic attack (TIA)
Basilar artery TIA
Sleep disorders
Narcolepsy/cataplexy
Benign sleep myoclonus
Movement disorders
Tics
Nonepileptic myoclonus
Paroxysmal choreoathetosis
Special considerations in children
Breath-holding spells
Migraine with recurrent
abdominal pain and cyclic
vomiting
Benign paroxysmal vertigo
Apnea
Night terrors
Sleepwalking
Features That Distinguish Generalized Tonic-Clonic Seizure from Syncope
Features
Seizure
Syncope
Immediate precipitating
factors
Usually none
Emotional stress, Valsalva,
orthostatic hypotension,
cardiac etiologies
Premonitorysy mptoms
None or aura (e.g., odd odor)
Tiredness, nausea,
diaphoresis,
tunneling of vision
Posture at onset
Variable
Usually erect
Transition to
unconsciousness
Often immediate
Gradual over seconds
Duration of unconsciousness
Minutes
Seconds
Duration of tonic or clonic
movements
30–60 s
Never more than 15 s
Features That Distinguish Generalized Tonic-Clonic Seizure from Syncope
Features
Seizure
Syncope
Facial appearance during
event
Cyanosis, frothing at
mouth
Pallor
Disorientation and
sleepiness
after event
Many minutes to hours
5 min
Aching of muscles after
event
Often
Sometimes
Biting of tongue
Sometimes
Rarely
Incontinence
Sometimes
Sometimes
Headache
Sometimes
Rarely