Essentials of Diagnosis
• Recurrent seizures.
changes accompany seizures.
• Mental status abnormalities or
focal neurologic symptoms may
persist for hours postictally.
The term "epilepsy" denotes any
disorder characterized by recurrent
A seizure is a transient disturbance
of cerebral function due to an
abnormal paroxysmal neuronal
discharge in the brain.
Epilepsy is common, affecting
approximately 0.5% of the population
in the United States
This category encompasses a broad
range of disorders, for which the age at
onset ranges from the neonatal period
to adolescence or even later in life.
Monogenic disorders tend to exhibit an
autosomal dominant pattern of
inheritance, and where the mutation is
known, the responsible gene often
encodes a neuronal ion channel.
There are many causes for recurrent
Withdrawal from alcohol or drugs.
Hypoglycemia or hyperglycemia
Since these seizures are provoked by a
readily reversible cause, this would not
be considered epilepsy
An important cause of seizures at any age especially in
Posttraumatic epilepsy is more likely to develop if the
dura mater was penetrated and generally becomes
manifest within 2 years following the injury.
However, seizures developing in the first week after
head injury do not necessarily imply that future attacks
There is no clear evidence that prophylactic
anticonvulsant drug treatment reduces the incidence of
Tumors and other space-occupying lesions
Neoplasms may lead to seizures at any age
Especially important cause of seizures in middle and
Seizures are commonly the initial symptoms of the
often are focal in character.
They are most likely to occur with structural lesions
involving the frontal, parietal, or temporal regions.
Tumors must be excluded by imaging studies (MRI
preferred over CT) in all patients with onset of seizures
after 30 years of age, focal seizures or signs, or a
progressive seizure disorder.
Become increasingly frequent causes of
seizures with advancing age
Are the most common cause of seizures with
onset at age 60 years or older
Alzheimer disease and other degenerative
disorders are a cause of seizures in later life.
Must be considered in all age groups
potentially reversible causes of seizures.
Seizures may occur with an acute infective or inflammatory
Bacterial meningitis or herpes encephalitis
or in patients with more longstanding or chronic
disorders, such as neurosyphilis or cerebral cysticercosis.
In patients with AIDS, they may result from central nervous
system toxoplasmosis, cryptococcal meningitis, secondary viral
encephalitis, or other infective complications.
Seizures are a common sequela of supratentorial brain
abscess, developing most frequently in the first year after
In many cases, the cause of epilepsy
cannot be determined.
Pediatric age groups
Congenital abnormalities and
perinatal injuries may result in
seizures presenting in infancy
Classification of Seizures
The International League Against Epilepsy
distinguishes seizures affecting only part of the
brain (focal seizures) from those that are
Other Associated Features
Involvement of only a restricted
part of brain; may evolve to a
bilateral, convulsive seizure
Observable focal motor or autonomic
symptoms, or subjective sensory or
psychic symptoms may occur
Above symptoms may precede,
accompany, or follow the period of
Diffuse involvement of brain at
Consciousness impaired briefly;
May have clonic, tonic, or atonic (ie,
patient often unaware of attacks
loss of postural tone) components;
autonomic components (eg, enuresis);
or accompanying automatisms
Almost always begin in childhood and
frequently cease by age 20
May be more gradual in onset
More marked changes in tone may
and termination than typical
Single or multiple myoclonic
Tonic phase: Sudden loss of
May be accompanied by tongue biting,
consciousness, with rigidity and
incontinence, or aspiration; commonly
arrest of respiration, lasting < 1
followed by postictal confusion
variable in duration
Clonic phase: Jerking occurs,
usually for < 2–3 minutes
Flaccid coma: Variable duration
Repeated seizures without
recovery between them; a fixed
and enduring epileptic condition
lasting ≥ 30 minutes
The initial clinical and EEG manifestations of
partial seizures indicate that only a restricted part
of one cerebral hemisphere has been activated.
The ictal manifestations depend on the area of
the brain involved
Focal seizures sometimes involve impairment of
consciousness and may evolve to convulsive
seizures, in a process previously called secondary
Without impairment of consciousness
Seizures may be manifested by focal motor symptoms
Somatosensory symptoms (eg, paresthesias or tingling) that
spread (or “march”) to different parts of the limb or body
depending on their cortical representation
Were previously described as “simple partial” seizures
In other instances, special sensory symptoms (eg, light
flashes or buzzing) indicate involvement of
visual, auditory, olfactory, or gustatory regions of the brain
There may be autonomic symptoms or signs (eg, abnormal
epigastric sensations, sweating, flushing, pupillary dilation).
The sole manifestations of some seizures are phenomena
such as dysphasia, dysmnesic symptoms (eg, déjà vu, jamais
vu), affective disturbances, illusions, or structured
hallucinations, but such symptoms are usually accompanied
by impairment of consciousness.
With impairment of consciousness
Impaired consciousness or responsiveness
may be preceded, accompanied, or followed
by the various symptoms mentioned above
Automatisms may occur.
Such dyscognitive seizures were previously
called "complex partial" seizures.
There are several different varieties of
In some circumstances, seizures cannot
be classified because of incomplete
information or because they do not fit
into any category.
These are characterized by impairment of consciousness, sometimes
with mild clonic, tonic, or atonic components (ie, reduction or loss of
postural tone), autonomic components (eg, enuresis)
Or accompanying automatisms
Onset and termination of attacks are abrupt
If attacks occur during conversation, the patient may miss a few words
or may break off in midsentence for a few seconds
The impairment of external awareness is so brief that the patient is
unaware of it
Absence ("petit mal") seizures almost always begin in childhood and
frequently cease by the age of 20 years or are then replaced by other
forms of generalized seizure
Electroencephalographically, such attacks are associated with bursts of
bilaterally synchronous and symmetric 3-Hz spike-and-wave activity
A normal background in the electroencephalogram and normal or
above-normal intelligence imply a good prognosis for the ultimate
cessation of these seizures.
Atypical absence seizures
There may be more marked changes in tone, or attacks may
have a more gradual onset and termination than in typical
They commonly occur in patients with multiple seizure types
May be accompanied by developmental delay or mental
Are associated with slower spike-wave discharges than those in
typical absence attacks.
Myoclonic seizures consist of single or multiple myoclonic jerks.
Tonic-clonic ("grand mal") seizures
In these seizures, which are characterized by sudden loss of consciousness
the patient becomes rigid and falls to the ground
respiration is arrested.
This tonic phase, which usually lasts for < 1 minute, is followed by a clonic phase in which
there is jerking of the body musculature that may last for 2 or 3 minutes
followed by a stage of flaccid coma
During the seizure, the tongue or lips may be bitten, urinary or fecal incontinence may occur
the patient may be injured.
Immediately after the seizure, the patient may recover consciousness, drift into sleep, have a
further convulsion without recovery of consciousness between the attacks (status
or after recovering consciousness have a further convulsion (serial seizures).
In other cases, patients will behave in an abnormal fashion in the immediate postictal
period, without subsequent awareness or memory of events (postepileptic automatism).
Headache, disorientation, confusion, drowsiness, nausea, soreness of the muscles, or some
combination of these symptoms commonly occurs postictally.
Tonic, clonic, or atonic seizures
Loss of consciousness may occur with either the tonic or clonic accompaniments
described above, especially in children.
Atonic seizures (epileptic drop attacks) have also been described.
Symptoms and Signs
Nonspecific changes such as headache, mood alterations, lethargy, and myoclonic jerking alert
some patients to an impending seizure hours before it occurs.
These prodromal symptoms are distinct from the aura; the aura that may precede a generalized
seizure by a few seconds or minutes is itself a part of the attack and it arises locally from a
restricted part of the brain
In most patients, seizures occur unpredictably at any time and without any relationship to posture
or ongoing activities
Occasionally, however, they occur at a particular time (eg, during sleep) or in relation to external
precipitants such as lack of sleep, missed meals, emotional stress, menstruation, alcohol ingestion
(or alcohol withdrawalbelow), or use of certain drugs
Fever and nonspecific infections may also precipitate seizures in epileptic patients.
In a few patients, seizures are provoked by specific stimuli such as flashing lights or a flickering
television set (photosensitive epilepsy), music, or reading.
No abnormality between seizures in patients with idiopathic epilepsy
In the immediate postictal period, extensor plantar responses may be seen
The presence of lateralized or focal signs postictally suggests that seizures may have a focal origin
In patients with symptomatic epilepsy, the findings on examination will reflect the underlying
MRI is indicated for patients with focal neurologic symptoms or
signs, focal seizures, or electroencephalographic findings of a focal
some clinicians routinely order MRI for all patients with new-onset
CT is generally less sensitive than MRI to small structural brain
abnormalities but may be used when MRI is contraindicated (eg, in a
patient with a metallic implant).
Such studies should be performed in patients with clinical evidence of a
progressive disorder and in those with new onset of seizures after the
age of 20 years because of the possibility of an underlying neoplasm.
Laboratory and Other Studies
Initial investigations should include complete blood count
serum glucose, electrolytes, creatinine, calcium, magnesium
liver function tests to exclude various causes of seizures and to
provide a baseline for subsequent monitoring of long-term effects of
A lumbar puncture may be necessary when any sign of infection is
present or in the evaluation of new-onset seizures in the acute setting
Electroencephalography may support the clinical diagnosis of epilepsy
(by demonstrating paroxysmal abnormalities containing spikes or
sharp waves), provide a guide to prognosis, and help classify the
Classification of the disorder is important for determining the most
appropriate anticonvulsant drug with which to start treatment
For example, absence and focal seizures with impairment of
consciousness may be difficult to distinguish clinically, but the
electroencephalographic findings and treatment of choice differ in
these two conditions.
Finally, by localizing the epileptogenic source, the
electroencephalographic findings are important in evaluating
candidates for surgical treatment.
The distinction between the various disorders
likely to be confused with generalized seizures is
usually made on the basis of the history.
The importance of obtaining an eyewitness
account of the attacks cannot be
Differential Diagnosis of Focal Seizures
Transient ischemic attacks
These attacks are distinguished from seizures by their longer
duration, lack of spread, and symptoms
Level of consciousness, which is unaltered, does not distinguish
There is a loss of motor or sensory function (eg, weakness or
numbness) with transient ischemic attacks, whereas positive
symptoms (eg, convulsive jerking or paresthesias) characterizes
Rage attacks are usually situational
lead to goal-directed aggressive
These may be hard to distinguish from focal
seizures unless there is evidence of an
anxiety disorder between attacks
attacks have a clear relationship to external
Differential Diagnosis of Generalized Seizures
Syncopal episodes usually occur in relation to postural
change, emotional stress, instrumentation, pain, or straining
They are typically preceded by pallor, sweating, nausea, and
malaise and lead to loss of consciousness accompanied by
flaccidity; recovery occurs rapidly with recumbency, and there is
no postictal headache or confusion
In some instances, however, motor accompaniments and urinary
incontinence may simulate a seizure.
Cerebral hypoperfusion due to a disturbance of cardiac
rhythm should be suspected in patients with known
cardiac or vascular disease or in elderly patients who
present with episodic loss of consciousness
Prodromal symptoms are typically absent
Repeated Holter monitoring may be necessary to
establish the diagnosis
Monitoring initiated by the patient ("event monitor")
may be valuable if the disturbances of consciousness
A relationship of attacks to physical activity and the
finding of a systolic murmur are suggestive of aortic
Loss of consciousness is preceded or accompanied
by other brainstem signs
Basilar artery migraine and vertebrobasilar vascular
disease are discussed elsewhere in this chapter
Psychogenic nonepileptic seizure (PNES)
Simulates an epileptic seizure
PNES may occur due to a conversion disorder or malingering
Many patients also have true seizures or a family history of epilepsy.
Although a PNES tends to occur at times of emotional stress, this may also be the case
with true seizures.
Clinically, the attacks superficially resemble tonic-clonic seizures, but there may be
obvious preparation before a PNES.
Moreover, there is usually no tonic phase; instead, there may be an asynchronous
thrashing of the limbs, which increases if restraints are imposed and rarely leads to injury.
Consciousness may be normal or “lost,” but in the latter context the occurrence of goaldirected behavior or of shouting, swearing, etc, indicates that it is feigned.
Postictally, there are no changes in behavior or neurologic findings.
Often, clinical observation is insufficient to discriminate epileptic from nonepileptic
seizures. Video electroencephalographic monitoring may be helpful: epileptic
seizures, especially those involving altered consciousness, commonly involve scalp
electroencephalographic signs that coincide with a behavioral spell, whereas a PNES does
The serum level of prolactin has been found to increase dramatically between 15 and 30
minutes after a tonic-clonic convulsion in most patients, whereas it is unchanged after a
PNES. Serum creatine kinase levels also increase after a convulsion but not a PNES.
For patients with epilepsy, drug treatment is prescribed
with the goal of preventing further attacks and is usually
continued until there have been no seizures for at least 2
Epileptic patients should be advised to avoid situations
that could be dangerous or life-threatening if further
seizures should occur.
Legislation may require clinicians to report to the state
authorities any patients with seizures or other episodic
disturbances of consciousness; driving cessation for 6
months or as legislated is appropriate following an
Choice of medication
Drug selection depends on seizure type
The dose of the selected drug is gradually increased until seizures are controlled or side
effects prevent further increases
If seizures continue despite treatment at the maximal tolerated dose, a second drug is added
and the dose increased depending on tolerance; the first drug is then gradually withdrawn
In treatment of focal seizures, the success rate is higher with carbamazepine, phenytoin, or
valproic acid than with phenobarbital or primidone.
Gabapentin, topiramate, lamotrigine, oxcarbazepine, levetiracetam, zonisamide, lacosamide,
ezogabine, vigabatrin, and tiagabine are newer antiepileptic drugs used to treat focal
seizures. Felbamate is also effective for such seizures but, because it may cause aplastic
anemia or fulminant hepatic failure, should be used only in selected patients unresponsive to
other measures. Rufinamide is currently approved only for seizures in patients with LennoxGastaut syndrome, but it may be effective against seizures in a broader range of refractory
patients. For generalized or unclassified seizures, valproate is better tolerated than
topiramate and more efficacious than lamotrigine and is thus preferred for many patients;
however, the teratogenic potential of valproate makes its use undesirable in women of
childbearing age. All antiepileptics are potentially teratogenic, although the teratogenicity of
the newer antiseizure medications is less clear. Nevertheless, antiepileptic medication must
be given to pregnant women with epilepsy to prevent seizures, which can pose serious risk to
the fetus from trauma, hypoxia, or other factors. In most patients with seizures of a single
type, satisfactory control can be achieved with a single anticonvulsant drug. Treatment with
two drugs may further reduce seizure frequency or severity but usually only at the cost of
greater toxicity. Treatment with more than two drugs is almost always unhelpful unless the