REVIEW ARTICLE
Acute Symptomatic Seizures
A Clinically Oriented Review
Pedro Beleza, MD
Background: Acute symptomatic seizures are seizures closely related
to neurological or systemic insults and represent about 40% of all first
seizures. Diagnosis may be difficult to perform due to the subjectivity
involved in recognizing the severity of insult needed to provoke epi-
leptic seizures or in determining a clear temporal relationship. Appro-
priate therapeutic management, risk of developing epilepsy, and mortality
depend largely on the underlying disorder.
Review Summary: A general overview regarding definition, epi-
demiology, and causes of acute symptomatic seizures is provided.
Diagnosis, frequency, risk factors, pathophysiology, therapeutic man-
agement, and prognosis of acute symptomatic seizures related to each
insult individually are discussed. The insults considered are: acute
stroke, traumatic brain injury, central nervous system infections,
medication, alcohol and illicit drugs, electrolytic and metabolic disorders,
anoxic encephalopathy, eclampsia, reversible posterior leukoencephal-
opathy, and limbic encephalitis.
Conclusions: Operational diagnostic criteria have been recommended
by the International League Against Epilepsy and are based on tem-
poral relationship, severity, and type of insult. Antiepileptic drug
prophylaxis is recommended in severe head trauma, preeclampsia, and
possibly high-risk subarachnoid or intracranial hemorrhage. It is cru-
cial to rapidly identify all insults possibly involved, treat underlying
diseases, revert corrigible factors, and in case of central nervous system
involvement, use antiepileptic drugs during the acute period. Risk of
epilepsy is increased in patients with neurological insults but not with
metabolic disorders. Some refractory epilepsies in adults, mostly epi-
lepsy due to hippocampal sclerosis, are preceded by acute symptomatic
seizures related to selected insults occurring at a specific time. Mortality
rate is globally increased.
Key Words: acute symptomatic seizures, causes, risk factors,
treatment
(The Neurologist 2012;18:109–119)
DEFINITION OF ACUTE SYMPTOMATIC SEIZURE
An acute symptomatic seizure was defined in a recent
recommendation from the International League Against Epi-
lepsy (ILAE) as a clinical seizure occurring in close temporal
relationship with an acute central nervous system (CNS) insult,
which may be metabolic, toxic, structural, infectious, or in-
flammatory.1 Seizures related to tumors, formerly considered
as acute symptomatic2 are now considered progressive
From the Department of Neurology, EEG Unit, Espirito Santo Saude
Hospitals, Arrabida Hospital and Clipovoa, Póvoa de Varzim, Portugal.
The author declares no conflict of interest.
Reprints: Pedro Beleza, MD, Department of Neurology, EEG Unit, Espirito
Santo Saude Hospitals, Arrabida Hospital and Clipovoa, Rua Dom
Manuel I, 183, 4490-592 Povoa de Varzim, Portugal. E-mail: beleza.76
@gmail.com.
Copyright r 2012 by Lippincott Williams & Wilkins
ISSN: 1074-7931/12/1803-0109
DOI: 10.1097/NRL.0b013e318251e6c3
The Neurologist  Volume 18, Number 3, May 2012
symptomatic, because they occur in the context of an evolving
clinical condition.1 The definition of acute symptomatic seiz-
ure was created for use in epidemiologic studies.1 The concept
rests on an epileptic seizure being a symptom of an acute
cerebral disorder, affecting the brain primarily or secondarily.3
A seizure that meets the criteria for acute symptomatic should
still be classified as such even if there is also a remote sym-
ptomatic etiology or a preexisting epilepsy.1 Situation-related
seizures, a translation from the German “gelegenheitsanfalle,”
is a broader term that includes not only acute symptomatic
seizures but also febrile seizures and isolated provoked seiz-
ures related to situations not usually accompanied by seizures
(eg, sleep deprivation and stress).4 Accordingly, ILAE has
recently recommended using the term “acute symptomatic
seizure” instead of situation-related seizure.1 It is meaningful
to differentiate acute symptomatic seizures, febrile seizures,
and the ill-defined gray area of isolated provoked seizures.
Febrile seizures are symptoms of selected seizure disorders
with major genetic influences including: (1) febrile seizures of
childhood, a benign entity defined as the occurrence of seizures
accompanied by fever without CNS infection, in a child aged 6
months to 5 years5 and (2) febrile seizures plus, a chronic
epilepsy syndrome occurring when febrile seizures persist after
the sixth year of life or in combination with afebrile seizures,
usually generalized tonic-clonic seizures.6 Isolated provoked
seizures related to situations not usually accompanied by
seizures may possibly represent some especially mild genetic
epilepsies with insufficient epileptogenic ability to induce
unprovoked seizures.4 Provoked seizure is a term derived from
the categorization of seizures based on the presence or absence
(unprovoked seizures) of a presumed acute precipitating
insult.2 The current diagnostic scheme for epilepsies proposed
by ILAE does not mention the term “acute symptomatic seiz-
ures” but instead has included some examples, like alcohol with-
drawal (AW) seizures, drug or other chemically induced seizures,
and posttraumatic seizures, under the category of “seizures
not necessarily requiring a diagnosis of epilepsy.”7 Defining
acute symptomatic seizures on clinical grounds may be difficult,
as it implies recognizing the severity of insult required to pro-
voke seizures and the determination of a temporal relationship.
SEVERITY OF INSULT REQUIRED TO PROVOKE
SEIZURES
The severity of insult needed to provoke a seizure can be
understood considering 4 conceptual models: (1) acute disease
model (eg, progressive organic dysfunction) in which multiple
insults are needed to provoke a seizure; (2) chronic disease
model (eg, stroke, chronic renal failure) in which seizures
occur after a single insult in the context of chronic disease; (3)
unique insult model (eg, eclampsia) in which seizures happen
after a high-magnitude insult; and (4) genetic predisposition in
which seizures occur after an insult of relatively low intensity.8
www.theneurologist.org | 109
Beleza
DELAY BETWEEN INSULT AND SEIZURE
REQUIRED TO BE CONSIDERED AS AN ACUTE
SYMPTOMATIC SEIZURE
With regard to the temporal relationship needed for an
event to be considered an acute symptomatic seizure, it theo-
retically consists of the period until clinical stabilization of
disease, which is a subjective concept in clinical practice.
ILAE has conventionally considered: (1) the period of 1 week
in stroke, head trauma, or anoxic encephalopathy; (2) the ac-
tive phase in CNS infection or inflammatory disease, based on
persistent clinical, laboratorial, or imaging findings; (3) within
24 hours in documented severe selected metabolic derange-
ments; and (4) within 7 to 48 hours of the last drink in AW.1
REMOTE SYMPTOMATIC SEIZURES AND
EPILEPSY
Acute symptomatic seizures must be differentiated from
seizures occurring after the acute insult, the so-called remote
symptomatic seizures,2 because they differ in prognosis and
management. A recent study has shown that individuals whose
first seizures were acute symptomatic seizures were 80% less
likely to experience a subsequent unprovoked seizure but had
higher early mortality, compared with individuals with a first
remote symptomatic seizure when the etiology is stroke,
traumatic brain injury (TBI), and CNS infection.9 These dif-
ferences support the argument against the inclusion of acute
symptomatic seizures in the current definition of epilepsy. In
2005, ILAE described epilepsy as “a disorder of the brain
characterized by an enduring predisposition to generate epi-
leptic seizures,” which may include single seizures even if
acute symptomatic.10 However, it is unclear when epilepsy
should be considered as a first acute symptomatic seizure,
because the operational meaning of “enduring predisposition”
to have seizures is still under refinement. An operational def-
inition of “probable epilepsy” was proposed as being after 1
provoked seizure and clinical, electroencephalography (EEG),
imaging, genetic, or other evidence indicating greater than a
50% chance of having an unprovoked seizure.11 The risk of a
first unprovoked seizure at 10 years of follow-up after an acute
symptomatic seizure is 17% for structural causes, 17% for
encephalopathic ones, and even higher after status epilepticus
(SE) (41%), particularly if due to structural (45%) or ence-
phalopathic causes (57%).12 Further studies should clarify
whether postencephalopathic SE should be regarded as epi-
lepsy and managed accordingly. Also, the risk of subsequent
unprovoked seizure in patients with repetitive acute symptom-
atic seizures needs assessment.
EVALUATION OF A FIRST SEIZURE
The occurrence of a first seizure in an adult requires a
detailed evaluation aimed mainly at identifying provoking
factors that may be involved and to evaluate the risk of de-
veloping epilepsy. The patient’s history as well as physical and
neurological examination may disclose a probable cause of
seizure or an increased risk of seizure recurrence (if remote
symptomatic seizure or family history of epilepsy is present).
Routine testing for glucose, serum electrolytes, calcium, and
full blood count has been recommended in the emergency
department setting by some centers.13,14 Toxicology screening
may be helpful in specific clinical circumstances (recom-
mendation level U).15 Neuroimaging and routine EEG should
be considered as part of the neurodiagnostic evaluation (rec-
ommendation level B).15 Brain computed tomography (CT) or
magnetic resonance imaging (MRI) has a yield of about 10%,
110 | www.theneurologist.org
The Neurologist  Volume 18, Number 3, May 2012
which may lead to diagnosis of structural lesions and may have
some value in predicting the risk of seizure recurrence.15 In the
emergency department, CT is usually the procedure of choice
because of relative speed and its effectiveness in excluding
catastrophic problems that may require immediate attention.
MRI in the first seizure needs more exploration, although in
selected cases and in nonemergent situations, MRI could be
more sensitive than a CT scan to detect abnormalities in pa-
tients with single seizures.16 Routine EEG has a yield of about
29% of EEGs showing epileptiform activity, which predicts the
risk of seizure recurrence and allows an initial classification of
seizures.15 EEG may also suggest the presence (continuous d
slowing), localization, and nature (eg, periodic lateralized epi-
leptiform discharges in acute stroke or herpes simplex ence-
phalitis) of a brain lesion.17 A lumbar puncture is essential if
the clinical presentation is suggestive of an acute brain in-
fection. In other circumstances, the test may be misleading,
because a prolonged seizure itself can cause cerebrospinal fluid
pleocytosis.15
TREATMENT AND OUTCOME
Efficacy of acute symptomatic seizure treatment is
thought to depend on early determination of all reversible in-
sults and their rapid correction. Despite having biological
plausibility, this hypothesis has not yet been confirmed.
Patients with acute symptomatic seizure do not need to be treated
with antiepileptic drugs (AED) on a long-term basis, although
such treatment may be warranted on a short-term basis until
the acute condition is resolved.18 As acute symptomatic seiz-
ures reflect, at least partially, the severity of insult, it is un-
derstandable that their occurrence is generally associated with
a poor outcome.19 However, the direct influence of acute
symptomatic seizures on prognosis has not yet been specifically
addressed.
EPIDEMIOLOGY OF ACUTE SYMPTOMATIC
SEIZURES
Population-based studies showed that the cumulative risk
for acute symptomatic seizures from birth to 80 years of age is
3.6%20 and age-adjusted incidence is 29 to 39/100,000 person-
years.20,21 Acute symptomatic seizures represent 40% of total
seizures,20 40% of all first seizures,21 and 50% to 70% of SE
episodes.22 There is almost double the risk of acute symptomatic
seizures in males (5% until 80 y of age) over females (2.7%).20
This seems to reflect sex-related differences in incidence of un-
derlying conditions, such as head trauma, rather than any bio-
logical phenomenon.20 Acute symptomatic seizures are more
commonly seen at age extremes, such as epilepsy with an in-
cidence of 253/100,000 newborns/y and of 123/100,000 elders/y,
probably due to increased incidence of metabolic, infectious, and
encephalopathic disorders in the neonatal period and of stroke in
the elderly.20
CAUSES OF ACUTE SYMPTOMATIC SEIZURES
The main causes of acute symptomatic seizures are acute
stroke (16%), TBI (16%), CNS infection (15%), medication,
alcohol and illicit drugs (14%), electrolytic and metabolic dis-
orders (9%), encephalopathy (5%), and eclampsia (2%).20
Causes of acute symptomatic seizures through life show the
same distribution as the CNS pathology found across different
ages: (1) newborns—encephalitis, metabolic disorders, and en-
cephalopathy; (2) children—encephalitis and head trauma; (3)
adults—head trauma, medication or AW, stroke, brain tumors,
and eclampsia; and (4) elderly—stroke.20 Neurological and
r 2012 Lippincott Williams & Wilkins
The Neurologist  Volume 18, Number 3, May 2012 Acute Symptomatic Seizures: A Review

systemic insults will be individually discussed according to the
following topics: (1) frequency, risk factors (Table 1), patho-
physiology, and treatment considerations of acute symptomatic
seizures; (2) significance of acute symptomatic seizures in
prognosis of underlying disease and risk for developing epilepsy.
hemorrhage (SAH) 8% and intracerebral hemorrhage (ICH)
7.3%] compared with ischemic stroke (4.2%).42 A recent work
showed that hemorrhagic stroke and cortical lesion were in-
dependent predictors of acute symptomatic seizures.39 Acute
symptomatic seizures were found in 16.2% patients with ICH
and in 4.2% patients with ischemic stroke.39

NEUROLOGICAL INSULTS
SAH
Acute Stroke Acute symptomatic seizures correlate independently with
Acute symptomatic seizures after stroke occur in 2.4% to high blood volume in basal cisterns on initial brain CT43 [odds
6.3% of patients.38,39 Most seizures occur within 2 days, and ratio (OR) = 1.1, P = 0.05] but not with duration of loss of
almost half (43%) within 24 hours after stroke.25 Seizures are consciousness, Glasgow Coma Scale (GCS), presence of
mostly focal.23,40 Some generalized tonic-clonic seizures have aneurysm, or previous history of hypertension.19 Seizures
been reported, although they most probably represent a sec- possibly arise due to blood in cisterns that may have an irritant
ondary generalization.40 Accordingly, in animal models, the effect in the brain cortex44 and after early ischemic brain le-
seizure onset zone corresponds to ischemic penumbra.41 A pro- sions caused by arterial vasospasm.45 Most patients present
spective study revealed that the frequency of acute symptomatic generalized seizures,19 suggesting a large seizure onset zone,
seizures is almost twice in hemorrhagic stroke [subarachnoid most probably mesial and possibly involving the temporal and/
or frontal lobe with a fast spread to the remaining cortex.46
AEDs are recommended after first acute symptomatic seizures
and during the acute phase. Although there are no strict
TABLE 1. Risk Factors for Acute Symptomatic Seizures According guidelines, some centers suggest AED for 1 to 2 weeks for
to Different Insults patients who have had a single seizure and AED for 4 to 6
Insults Risk Factors Study weeks for the selected group of patients with recurrent seizures
or SE during hospital treatment.47
Subarachnoid High blood volume in basal cisterns Butzkueven The routine long-term use of anticonvulsants is not rec-
hemorrhage et al19
Intracerebral Temporal or parietal cortex; Faught
ommended (class III, level of evidence B) but may be con-
hemorrhage aneurysm, angioma, or neoplasm et al23 sidered for patients with risk factors such as prior seizure,
Weisberg parenchymal hematoma, infarct, or middle cerebral artery
et al24 aneurysms (class IIb, level of evidence 3B).48 The admin-
Ischemic stroke Clinically severe strokes, cortical Bladin istration of prophylactic AED may be considered in the im-
involvement et al25 mediate posthemorrhagic period (class IIb, level of evidence
Cerebral vein Aphasia or motor deficit; superior Ferro B),48 mostly in the presence of high blood volume in basal
thrombosis sagittal sinus and cortical vein; et al26,27 cisterns.19 Some concerns exist regarding phenytoin use in
parenchymal lesions seizure prophylaxis, because it has been associated with
CNS infections Encephalitis; herpes simplex or Kim et al28
neurocysticercosis; impairment of
a worsened cognitive and neurological outcome.49 Acute
consciousness (GCS r12 at symptomatic seizures represent an independent risk factor for
admission) late seizures (seizures occurring between 24 h and 6 wk)
Traumatic brain Children, loss of consciousness or Bruns and (OR = 27, P < 0.01) and are predictive of an unfavorable
injury amnesia >30 min, acute Hauser29 functional recovery (GCS) at 6 weeks (OR = 7.8, P = 0.04),
intracerebral hematomas or possibly being surrogate markers for severity of brain insult.19
subdural hemorrhages Late seizures occur in 2/3 of patients within the first 4 weeks
Medication Chlorpromazine, clozapine, Starkey and and correlate with rebleeding and high blood volume on initial
maprotiline, clomipramine, Lawson30 CT scan.50 Patients with SAH have a 34-fold increase risk of
bupropion, meperidine, Devinsky
flumazenil, cyclic antidepressants, et al31
developing epilepsy compared with the general population.51
theophylline, isoniazid, alkylating Delanty
antineoplastic agents, and et al8
cyclosporine; overdose of ICH
medication, intravenous Acute symptomatic seizures correlate with temporal or
administration; brain lesions; and parietal cortical involvement23,52 and to selected etiologies
renal or hepatic dysfunction such as aneurysm, angioma, or neoplasm.24 Seizures possibly
Illicit drugs Amphetamine-like agents overdose; Pascual- occur due to the presence of blood metabolism products,
cocaine, mostly in women, if Leone namely hemosiderin that seems to have epileptogenic activity
smoked et al32
Dhuna
similarly to that observed in rat models in whom focal epi-
et al33 lepsies are produced after iron injections into the brain cor-
Alldredge tex.53 AEDs are recommended after a first acute symptomatic
et al34 seizure and should be taken during the acute phase (1 to
Metabolic and Natremia <115 mg/dL; magnesemia Boggs35 2 wk).47 A brief period of prophylactic AED soon after ICH
electrolyte <0.8 mg/dL; calcemia <5 mg/dL; Whang onset may be considered, as it may reduce the risk of early
disorders glycemia <36 mg/dL; glycemia et al36 seizures in patients with lobar hemorrhage (class IIb, level of
>450 mg/dL associated with Gao et al37 evidence C).54 The occurrence of acute symptomatic seizures
ketoacidosis in patients with ICH does not influence functional or vital
CNS indicates central nervous system; GCS, Glasgow Coma Scale. outcome at 6 months.52 Risk of developing epilepsy after an
acute symptomatic seizure is 27% within 5 years.55

r 2012 Lippincott Williams & Wilkins www.theneurologist.org | 111

Beleza
Ischemic Stroke
Predictors for acute symptomatic seizures are clinically
severe infarcts (risk 2.10 times higher, applying Canadian
neurological score) and cortical involvement. Also, an asso-
ciation between extensive and hemorrhagic infarcts was
found.25,39 Although rare, acute seizures may occur during
a transient ischemic attack (TIA).56 The differential diagnosis
between TIA and seizures may be difficult to perform, for
example in shaking TIA57 and special seizures and in aphasic
or akinetic subtypes.58 In lacunar stroke, 2.6% of patients have
seizures40 probably related to concurrent cortical involvement
and not directly induced by lacunar stroke. Accordingly,
a population-based study showed that in 11 out of 13 patients
with seizures after lacunar stroke (diagnosed on CT scan
without apparent cortical ischemic lesion) MRI revealed as-
sociated ipsilateral posterofrontal or anterotemporal cortical
ischemic lesion. In addition, single-photon emission CT
showed hypoperfusion in the ipsilateral frontal area in all pa-
tients.59 Regarding the etiology of stroke, contrary to what was
previously thought, the risk for acute symptomatic seizures is
not increased in cardioembolic strokes.60 Acute brain ischemia
leads to a high concentration of extracellular glutamate that has
been shown to have the ability to produce recurrent epilepti-
form discharges in cultural hippocampal neurons.61 The Eu-
ropean Stroke Organization recommends AED to prevent
recurrence of seizures after stroke (class I, level A).62 A recent
study revealed that patients with early seizures (< 2 wk) had
low seizure recurrence rates (3%), which suggests that after an
acute symptomatic seizure a patient should be treated ex-
clusively during the first 2 weeks.63 Others argue that the de-
cision to treat after a first acute symptomatic seizure should be
individualized and be based on the functional consequences of
first seizure and the preferences of patient.64 The coadministra-
tion of recombinant tissue plasminogen activator and the drugs
levetiracetam, valproic acid (VPA), phenytoin, and phenobarbi-
tal seems to be safe and viable.65 Furthermore, seizures emerging
during thrombolysis are considered a good sign of restoration of
blood flow.66 Most of the first-generation AEDs, particularly
phenytoin, may not be the appropriate choice for these patients
based on its potential negative effect on functional recovery and
interaction with warfarin and salicylates.49 Also, salicylates
displace benzodiazepine and VPA from their plasma protein-
binding sites, which may lead to some decline in their total
plasma level.67 In contrast, the more recently developed AEDs,
including lamotrigine, gabapentin, pregabalin, oxcarbazepine,
topiramate, levetiracetam, zonisamide, and lacosamide do not
demonstrate significant interaction with anticoagulants or anti-
platelet agents. In elderly adults with focal onset seizures, la-
motrigine and gabapentin are recommended (level of evidence
A) as first-line monotherapy.68 Gabapentin remains the only
drug that has been specifically evaluated in stroke patients,
demonstrating a high rate of long-term seizure freedom (81% at
30 mo).69 Acute symptomatic seizures are possibly harmful for
ischemic penumbra due to additional metabolic stress involving
that vulnerable zone.70 Studies in animals showed that repeated
seizures in the context of brain ischemia increase infarct size and
may harm functional recovery.71 In humans, acute symptomatic
seizures correlated on univariate analysis with worse functional
prognosis at admission and follow-up (median of 9 mo) and
an increased mortality rate at 30 days and 1 year,25 although
severity of stroke was not a controlled variable.
Cerebral Venous Thrombosis (CVT)
In CVT, 40% of patients show seizures at presentation
of disease and a further 6.9% of patients have seizures within
112 | www.theneurologist.org
The Neurologist  Volume 18, Number 3, May 2012
2 weeks of the insult.72 Risk factors for seizures at presentation
of CVT are focal signs (aphasia, motor deficit), localization of
CVT (superior sagittal sinus and cortical vein), and paren-
chymal lesion, mainly if supratentorial.26,27 Most important
predictors for seizures occurring within 2 weeks are supra-
tentorial lesions as seen on CT/MRI at admission and seizures
at the presentation of CVT. Some studies suggest that AEDs
should be used for 2 weeks in patients with CVT and supra-
tentorial lesions who present seizures.72 A Cochrane Review
failed to find any evidence supporting the use of AEDs for the
primary prevention of seizures related to CVT.73 Acute
symptomatic seizures may lead to neurological and systemic
deterioration, SE, and death, although seizures have not been
shown to be an independent predictor of death and/or
dependency.26 There is a moderate risk of developing epilepsy
within 1 year after acute CVT seizures but later than that it is
rare.27
TBI
Acute symptomatic seizures occur in 6% of patients74
who experience a TBI. Risk factors for occurrence include age
(children), markers of severe lesion such as loss of con-
sciousness or amnesia for >30 minutes, and acute ICH or
subdural hematomas.29 A large randomized double-blind study
has shown that phenytoin exerts a beneficial effect by reducing
seizures only during the first week after severe head injury.75
This clinical trial has largely contributed to the American
Academy of Neurology recommendation for acute symptom-
atic seizure prophylaxis with phenytoin for 7 days after severe
TBI (level A).76,77 Carbamazepine has been evaluated in an-
other study, with results similar to those for phenytoin—a re-
duction in early seizures but no effect on epilepsy even during
the period of treatment.78 VPA has been evaluated in only 1
study, and the comparator was 1 week of phenytoin, making
the effect on early seizures difficult to interpret. The early
seizure rate was higher on VPA than on phenytoin, although
with the small numbers of early seizures, the difference is not
statistically significant. VPA showed no positive effect in re-
lation to late seizures.79 Independent risk factors for develop-
ing posttraumatic epilepsy are acute symptomatic seizures, >65
years of age, loss of consciousness or amnesia for >24 hours,
acute intracerebral hematomas, subdural hematomas, and brain
contusions.29 Severe TBI increases the risk of epilepsy by
about 17-fold, which translates into >15% of people with se-
vere TBI developing epilepsy.80 Adults with moderate to se-
vere TBI presented 9 times higher risk of epilepsy when acute
symptomatic seizures are associated. Differently, in children,
acute symptomatic seizures were not associated with an in-
creased risk of epilepsy.81 Mesial temporal lobe epilepsy (TLE)
may result from TBI in adolescents and adults and not ex-
clusively in children. It is frequently bilateral and includes
multifocal lesions.82 Posttraumatic epilepsy begins in most pa-
tients within the first year, although in severe TBI it may happen
up to 20 years later.80 What occurs in the brain during those
months or years is of great interest, because this period repre-
sents an opportunity for intervention with antiepileptogenic
therapies. As clinical trials show that treatment with conven-
tional AEDs (phenytoin, phenobarbital, carbamazepine, VPA, or
magnesium) after TBI does not protect against later development
of epilepsy,83 the identification of the cellular and molecular
changes involved in the cascade of events leading up to epilepsy
might reveal new therapeutic targets. Multiple experimental
models are revealing that there may be stepwise changes that
occur in the neuronal network over days to weeks, or even
months and years, after an epileptogenic insult. Early changes
r 2012 Lippincott Williams & Wilkins
The Neurologist  Volume 18, Number 3, May 2012
include the induction of immediate early genes and post-
translational modifications of neurotransmitter receptor and ion
channel/transporter proteins.84–86 Within days, neuronal death,
initiation of an inflammatory cascade, and new gene transcription
has been reported to occur.87,88 Later changes occurring over days
to weeks include anatomic changes including axonal sprouting
and dendritic modifications, such as the mossy fiber sprouting that
is commonly observed as a hallmark of the chronic epileptic
brain.89 Treatment trials with varying degrees of success have
included compounds that block glutamate receptors or calcium
channels, caspase inhibitors and antiapoptotic agents, and neu-
rotrophic factors, as well as stem cell transplantation.90 Although
there have been some positive results, these treatments have not
yet been translated to humans. An important reason for this dis-
connect is (1) the lack of available biomarkers in clinical use to
indicate underlying pathogenesis and (2) the unclear alignment
between animal models and human patients with respect to the
time-dependent mechanisms within the epileptogenic cascade.91
CNS Infection
Acute symptomatic seizures occur in 5% of patients with
acute CNS infection.81 Risk factors for occurrence include
encephalitis (14 times more than meningitis), etiology (eg,
herpes simplex, neurocysticercosis), age ( > 42 y of age) and
GCS r12 at admission.28 In herpes simplex encephalitis,
acute symptomatic seizures occur in 40% to 60% of patients,
reflecting virus tropism to the mesial temporal lobe.92 Neuro-
cysticercosis presents as acute symptomatic seizures when
imaging identifies at least 1 parasite in the transitional or de-
generative phase.93 Although new-onset seizures may occur
during calcified cystic stage, chronic epilepsy is generally at-
tributed to this cyst stage.94 Seizures may occur in acute CNS
infection setting mediated by proinflammatory cytokines such
as IL-1 and tumoral necrosis factor87 that, in a culture of
hippocampal neurons, inhibit g-aminobutyric acid (GABA)
receptors and lower seizure threshold.95 AEDs are commonly
used after first acute symptomatic seizures during the acute
phase. Risk factors for developing epilepsy depend on the
existence of acute symptomatic seizures, type of CNS in-
fection, and imaging findings. The risk for epilepsy is 22% for
patients with viral encephalitis and acute symptomatic seiz-
ures, 10% for patients with viral encephalitis without acute
symptomatic seizures, 13% for patients with bacterial menin-
gitis and acute symptomatic seizures, 2.4% for patients with
bacterial meningitis without acute symptomatic seizures, and
2.1% for patients with aseptic meningitis.81 Persistent neuro-
cysticercosis abnormalities on brain CT, namely persistent
cysts and calcified cysts, show a 56% and 52% risk of recurrent
seizures, respectively.96 That is the reason why some authors
recommend monitoring cyst activity with CT scanning and
continuation of AEDs until resolution of the acute lesion.96
Epilepsy usually begins within 5 years, although it can occur
20 years after CNS infection. Neurocysticercosis is the most
common cause of epilepsy in developing countries, where it
accounts for up to 30% of all seizures.97 Refractory epilepsies
developed after CNS infections are predominantly multifocal98
and temporal lobe epilepsies. Multifocal epilepsies usually
occur after severe encephalitis with diffuse brain lesions. TLE
may develop if CNS infection occurs at young ages or if the
etiologic agent involved presents tropism for this lobe. Acute
meningitis or encephalitis occurring before 4 years of age are
more commonly related to hippocampal sclerosis (HS), and
when occurring after this age, they are more frequently asso-
ciated with extrahippocampal neocortical epilepsy, rarely with
abnormalities on brain MRI.99 In elderly subjects, the hippo-
r 2012 Lippincott Williams & Wilkins
Acute Symptomatic Seizures: A Review
campus is more resistant to lesions, requiring more severe
insults to produce an epileptogenic zone. Other studies have
shown that a previous history of meningitis or encephalitis at
an early age (r4 y of age) is a predictor of excellent surgical
outcome after anterior temporal lobectomy, independently of
the presence of HS on preoperative MRI.100 Some reports have
shown that nonfulminant herpetic encephalitis may be a cause
of HS.101 Recently, the association between human herpes
virus (HHV)-6 infection, complex febrile seizures, and devel-
opment of TLE has been under investigation. Occurrence of
HHV-6 infection coincides with the incidence peak of complex
febrile seizures. Some studies have shown that 2/3 of patients
with HS who underwent temporal lobectomies present ac-
tive replication of HHV-6B, which does not occur in other
causes of epilepsy.102 This working hypothesis has yet to be
confirmed.
DISEASES WITH SYSTEMIC INVOLVEMENT
Medication, Alcohol, and Illicit Drugs
Medication
Acute symptomatic seizures may occur after use or
withdrawal of medication.2 Risk of medication-related seizures
depends on medication type (intrinsic epileptogenicity), and on
dose and factors intrinsic to the patient (brain lesions and renal
or hepatic dysfunction).35 Concrete knowledge of the risk of
seizures related to different medications is based on level 4
evidence. Medications related to a moderate risk of seizures
are chlorpromazine, clozapine,31 maprotiline, clomipramine,
bupropion, meperidine, and flumazenil.35 A particularly high
risk of seizures is seen in overdose of cyclic antidepressants
(up to 20% of patients)30 (especially amoxapine and maproti-
line), theophylline, isoniazid, alkylating antineoplastic agents,
and cyclosporine.35 Factors involved in serum and brain levels
of medication include high dosage, intravenous (IV) admin-
istration, and intrinsic properties of medication affecting de-
gree of penetration into CNS, such as lipid solubility, molecular
weight, ionization, and protein binding.35 Mechanisms re-
sponsible for medication-related seizures are well understood
for antibiotics, which represent an intermediate risk of seiz-
ures.35 Penicillin, which has been used to create animal models
of epilepsy,103 prevents GABA from binding to the GABAA
receptor.104 Cephalosporins, imipenem, and fluoroquinolones
antagonize GABAA receptors. Isoniazid competes with pyr-
idoxine, which is usually transformed into pyridoxal phosphate,
a cofactor for GABA synthesis, thus leading to a decrease in
GABA levels.105 Treatment of seizures related to neuroleptics
and antidepressants consists primarily of reducing dosage or
changing to an alternative medication with a lower risk of
seizures such as haloperidol, risperidone, selective serotonin
reuptake inhibitors, or monoamine oxidase inhibitors.106 Seiz-
ures can be a feature of withdrawal from barbiturates, benzo-
diazepines, and other sedatives including meprobamate, chloral
hydrate,107 and zolpidem.108 Downregulation of GABA re-
ceptors is probably the mechanism involved.109 Either with
barbiturates or benzodiazepines, withdrawal seizures are dose
related and are unlikely in patients taking recommended ther-
apeutic doses.109,110 Short-acting barbiturates (eg, pentobarbi-
tal, secobarbital, amobarbital, and butalbital) are most likely to
produce seizures between day 1 and day 5 after intake discontin-
uation; full-blown delirium tremens sometimes follows.111 Seizures
during benzodiazepine withdrawal usually occur within 24 hours of
stopping a short-acting agent and within several days of stopping a
long-acting agent.112 A Cochrane review concluded that gradual
www.theneurologist.org | 113
Beleza
tapering (over 10 wk) of benzodiazepines was preferable to abrupt
discontinuation. Switching from short half-life benzodiazepine to
long half-life benzodiazepine before gradual taper withdrawal did
not receive much support from this study. Carbamazepine might
have promise as an adjunctive medication for benzodiazepine
withdrawal, particularly in patients receiving benzodiazepines in
daily dosages of 20 mg/d or more of diazepam (or equivalent).113
Furthermore, withdrawal of any anticonvulsant and narcotic drugs
(eg, morphine, propoxyphene, midazolam, meperidine) can give
rise to seizures.114
Alcohol
Acute symptomatic seizures may occur after AW or acute
intoxication and represent 1/3 of total hospital admissions due
to seizures.115 A study showed that of all patients (n = 140) at
first considered as presenting alcohol-related seizures, 54% had
seizures of other etiologies: head injury (26%), idiopathic
(16%), cerebrovascular accident (6%), lesion (4%), and tox-
icity (3%).116 Indicators of AW seizures include: history of
chronic alcohol abuse, history of current alcohol use with re-
cent reduction in consumption, and generalized tonic-clonic
seizure with other symptoms of withdrawal such as tremors,
sweats, or tachycardia (generally beginning within 5 to 10 h of
decreasing ethanol intake); the seizure must occur within 7 to
48 hours of the last drink.93 AW seizures usually occur either
as an isolated event or in brief clusters, although in <10% of
patients they may present as SE. Seizures are more commonly
generalized and characteristically show normal interictal
EEG.117 Acute alcohol ingestion has an inhibitory effect on
N-methyl-D-aspartate (NMDA) receptors, reducing excitatory
glutamatergic transmission, and has an agonistic effect on
GABAA receptors. In chronic alcohol abuse, NMDA receptors
are upregulated and GABAA receptors are downregulated,
leading to tolerance. The roles are reversed during abstinence,
with enhanced NMDA receptor function and reduced GA-
BAergic transmission, leading to many of the symptoms and
signs of acute withdrawal syndrome, including seizures.118
Studies in animals revealed that the seizure onset zone is lo-
cated in the brainstem probably in the inferior colliculus119 and
also involves the amygdale120 but not the neocortex. AW
seizures must be promptly treated, because the risk of re-
currence within the same withdrawal episode is about 13% to
24%.121 The only known factor associated with lower seizure
recurrence is serum ethanol levels >100 mg/dL.122 In primary
prevention of seizures in AW and for treatment of the AW
syndrome, benzodiazepines (lorazepam or diazepam) should
be chosen (level A recommendation).123 They have a phar-
macological profile similar to ethanol, enhancing GABAergic
transmission in the CNS. Benzodiazepines (diazepam or lor-
azepam) are also recommended after the first seizure, including
SE (level A recommendation).123 Some evidence exists that
carbamazepine, oxcarbazepine, and topiramate may be as ef-
ficacious as benzodiazepines.124 A mortality rate of <3% has
been attributed to AW seizures.125
Illicit Drugs
Seizures are considered as acute symptomatic based on
the probability of seizure occurrence for specific drugs.93 There
is high probability of cocaine involvement if metabolites are
found in urine or blood and for amphetamine-like agents (eg,
dextroamphetamine, methylphenidate, ephedrine, and meth-
amphetamine) if taken in excess.93 Cocaine-related seizures
occur in 9.3% of subjects,32 mostly in women (3 times more
frequent than men),33 immediately or within hours after drug
abuse, particularly if smoked (when it reaches higher serum
114 | www.theneurologist.org
The Neurologist  Volume 18, Number 3, May 2012
levels than if inhaled), and not necessarily with concomitant
overdose signs.32 Amphetamine-like–related seizures are often
accompanied with other signs of overdose (fever, hypertension,
cardiac arrhythmias, delirium, or coma).34 There is fair prob-
ability of seizure occurrence after hallucinogens.93 In North
America and Europe, the most popular hallucinogens are
peyote cactus containing mescaline, mushrooms containing
psilocybin and psilocin, and the synthetic ergot derivative
D-lysergic acid diethylamide. The visual illusions and halluci-
nations produced by these agents are not considered epilepti-
form,126 but true seizures can follow very high doses.127 Heroin
overdose, with coma, pinpoint pupils, and respiratory depres-
sion, is sometimes associated with seizures, but their occur-
rence in this setting is so unusual that other possible causes
such as concomitant cocaine use, ethanol withdrawal, or CNS
infection should be sought.107 Drug-related seizures are mostly
generalized but if focal may represent a cocaine-related
stroke.128 Current or previous heroin abuse carries a 2.6 times
higher risk for developing epilepsy.129
Electrolytic and Metabolic Disorders
Electrolytic disorders are frequently found in clinical
practice though are rarely associated with seizures. The more
rapid the disturbance develops the more likely it is to induce
seizures.130 Finding an electrolytic disorder in a patient with
a first seizure should not preclude the investigation of other
possible causes. Acute symptomatic seizures are operationally
defined based on the blood sample obtained within 24 hours of
the seizure, when it is logical to assume that the findings are
similar to those at the time of the seizure.93 In a literature
search of studies of electrolytic disorders and seizures, only
case studies were found, and in these, the biochemical ab-
normalities were mostly reported as group means with standard
deviations. Cutoffs at the extreme end of abnormalities fa-
voring specificity over sensitivity have been provided by the
subcommission on definitions for acute symptomatic seizure.93
Accordingly, seizures may occur in hyponatremia (< 115 mg/
dL), especially when a rapid decrease of serum sodium
occurs.35 Hypernatremia may cause seizures specially during
rehydration, and it is recommended that sodium concentration
is reduced at a rate below 0.5 mmol/L/ h to prevent seizures.131
Hypomagnesemia (< 0.8 mg/dL) and hypocalcemia (< 5.0 mg/
dL) predispose patients to seizures.36 Hypoglycemia (< 36 mg/
dL) causes seizures by mechanisms similar to those of cerebral
hypoxemia. Damage is greatest at the same levels of the cer-
ebral cortex, hippocampus, striatum, and cerebellum that are
most vulnerable to hypoxia.35 Nonketotic hyperosmolar coma
more commonly results in seizures than does diabetic ketoa-
cidosis (glycemia >450 mg/dL associated with ketoacidosis),
probably due to the anticonvulsant effect of ketosis.37 When
there is suspicion that the seizure may be acute symptomatic
due to a metabolic derangement but the proposed cutoffs are
not met, seizures should not be classified as acute symptomatic
but instead be placed into an “unknown” category but excluded
as epilepsy.93 Better cutoffs will require specific studies in the
future. Regarding treatment, it is necessary to rectify the un-
derlying disorder, and AED treatment is usually not needed.132
Anoxic Encephalopathy
Anoxic encephalopathy after cardiorespiratory arrest may
cause early seizures in 36% of patients. Myoclonic and tonic-
clonic seizures are the predominate seizure types.133 Most
relevant studies on prognosis of postanoxia myoclonic status
have defined myoclonic status based only on semiology
and not on EEG134,135 that, although it does not permit
r 2012 Lippincott Williams & Wilkins
The Neurologist  Volume 18, Number 3, May 2012
confirmation of the epileptic nature of the myoclonus thereby
allowing it be considered as an “acute symptomatic seizure,” it
also does not exclude it. According to those studies, myoclonic
status within 24 hours of the insult is regarded as a strong
predictor of poor vital and functional outcome, including
persistent vegetative state (recommendation level B),136 al-
though at least 8 patients did have a satisfactory outcome,
being able to walk, interact, or even return to baseline.137–140
All these patients had myoclonic SE after cardiorespiratory
arrest secondary to acute respiratory difficulties, rather than
primary cardiac events, raising the possibility that metabolic
changes before the arrest might limit anoxic brain damage and
favor recovery.141 A recent work identified preserved brain-
stem reactions, somatosensory evoked potentials, and EEG
reactivity as favorable predictors for awakening beyond veg-
etative state in postanoxic SE provided that SE was treated
vigorously.142 Further studies are needed to evaluate the ben-
efit of treating this subgroup of patients as SE. VPA, clona-
zepam, piracetam, and levetiracetam have proved efficacious
in the treatment of cortical myoclonus.143 Continuous gener-
alized periodic pattern (PP) is a common EEG endpoint of
advanced coma, particularly after cerebral hypoxia.144 PP is
recognized as a nonconvulsive status epilepticus (NCSE) when
EEG or clinical improvement occurs after IV benzodiaze-
pines.145 PP is of less clear significance if no clinical or EEG
regression happens after IV benzodiazepines; some authors
regard PP as a sign of severe encephalopathy and others still
consider it as possibly epileptic.146 The prognosis of comatose
NCSE with regard to survival or regaining a meaningful life is
dismal in the overwhelming number of cases.147 A synergistic
effect of ischemic brain injury and electrical SE on mortality
has been suggested.148 All patients with comatose NCSE and
coma-PP (PP without NCSE criteria) with mechanical ven-
tilation are under generalized anesthesia that includes an an-
tiepileptic effect (none of these patients is left untreated). In
comatose NCSE and coma-PP with sufficient spontaneous
respiration, a treatment trial with sufficient IV doses of an AED
has been pragmatically proposed, although AEDs may increase
the risk of additional sedation and respiratory depression.146
Positive results are rare as 1 study showed that only 2 of 33
comatose NCSE patients improved with AEDs.149 If the re-
sponse leads to electrographic and clinical improvement, the
AED treatment should be continued.146 Less severe chronic
brain hypoxia like sleep apnea or chronic obstructive pulmo-
nary disease is associated with an exacerbation of seizures in
adults138 and may also predispose them toward seizures.
Eclampsia
Eclampsia is defined as the occurrence of seizures during
gestational hypertension ( > 20 wk) with proteinuria ( > 300 mg/
24 h),150 seen in 5% to 10% of pregnant whites.151 Seizures
may occur postpartum up to the sixth week (55% of patients),
prepartum (45% of patients), and during partum (5% of pa-
tients).152 Seizures are usually preceded by visual disturbances
(50%), headache (19%) or epigastralgia (19%) and not nec-
essarily by signs of preeclampsia (arterial hypertension or
proteinuria) (38%).153 Seizures are usually attributed to brain
edema secondary to brain vasodilatation after autoregulation
loss provoked by a rapid increase in arterial hypertension. MRI
typically shows vasogenic edema in parietooccipital areas.154
Some clinical findings, such as normal arterial tension or ab-
sence of papilledema, challenge the theory that the cited
mechanism is the only physiopathology involved. Accord-
ingly, it has been proposed recently that uteroplacental ische-
mia causes the release of neurokinin B, inflammatory
r 2012 Lippincott Williams & Wilkins
Acute Symptomatic Seizures: A Review
cytokines, endothelins, and tissue plasminogen activator that
stimulate excitatory neuronal receptors independently of vas-
cular effects.155 Magnesium sulfate is effective in preventing
eclampsia reducing by half the risk of seizures in patients with
preeclampsia.156 In addition, magnesium sulfate is recom-
mended in the treatment of eclampsia, as it has been shown to
be more effective in decreasing seizure recurrence than dia-
zepam or phenytoin.157 It acts through decreasing peripheral
vascular resistance, limits vasogenic edema, and centrally in-
hibits NMDA receptors, providing anticonvulsant activity by
increasing the seizure threshold.158 Prenatal exposure to pre-
eclampsia or eclampsia is a risk factor for epilepsy among
children born at term.159 Furthermore, eclampsia may be a risk
factor for TLE-HS. About 1/3 of women who underwent
temporal lobectomy due to TLE-HS and without other known
risk factors for HS started epilepsy 1 month to 2 years after
eclampsia. The possible mechanism involved is vaso-
constriction of posterior circulation with subsequent hippo-
campal ischemia after acute hypertension.160
Reversible Posterior Leukoencephalopathy (RPL)
RPL is characterized by imaging findings of subcortical
vasogenic edema (T2, DWI, and ADC hyperintensity) with
preferential parietooccipital involvement and subsequent res-
olution. Major etiologies involved are hypertensive emer-
gency, eclampsia, and use of immunosuppressive or cytotoxic
agents.161 Seizures are a frequent presentation of RPL (87%),
mostly isolated (63%), although SE may occur.161 Occipital
seizures are the predominant seizure type.162 Pathophysiology
involved is known for RPL of hypertensive etiology in which,
like eclampsia, rapidly increasing arterial tension beyond
certain levels (160/100 mm Hg in normotensives or 220/
110 mm Hg in hypertensives) leads to a loss of autoregulation
with subsequent vasodilatation and edema. Preferential in-
volvement of posterior circulation is hypothesized to occur due
to scarce sympathetic innervation.163 AED are used after the
first seizure and during acute episodes of RPL. Most patients
with acute symptomatic seizures do not progress to epi-
lepsy.161 One study reported 3 patients with hypertensive en-
cephalopathy of childhood onset who developed TLE-HS in
the following months to years.164
Limbic Encephalitis (LE)
Clinical features of LE include a recent onset (usually
within days or weeks) of seizures, anterograde amnesia, or
affective disturbances with a prominent lability of mood and
lack of inhibition. In addition, to establish the diagnosis, one of
the following additional features must be observed: neoplasm,
LE-associated autoantibodies, temporomedial fluid attenuated
inversion recovery/T2 signal hyperintensity on MRI that is not
otherwise explainable, or a chronic lymphocytic-microglial LE
demonstrated on histopathology. LE-associated antibodies may
be directed against classic paraneoplastic antigens (Hu, Ma2,
CV2/CRMP5, and amphiphysin) or cell membrane antigens
(voltage-gated potassium channels, NMDA receptor, and oth-
ers pending characterization).165 Whereas the disorders related
to the first category of antibodies are associated with cancer
(lung, testis and other), prominent brain infiltrates of cytotoxic
T cells, and limited response to treatment, the disorders related
to the second category of antibodies associate less frequently
with cancer (thymoma, teratoma), seem to be antibody medi-
ated, and respond significantly better to immunotherapy.166
Seizures occur in 90% of patients with LE with antibodies to
cell membrane antigens, either voltage-gated potassium
channel or other cell membrane antigens167,168 and in 50% of
www.theneurologist.org | 115
Beleza
patients with paraneoplastic LE.169 Brain MRI shows a typical
evolution in all LE subtypes and is characterized by T2/fluid
attenuated inversion recovery hyperintensity (representing
vasogenic edema) in the mesial temporal lobe within the first
weeks and months of disease (occasionally it may persist for
years), followed by edema reversion associated with persistent
hyperintensity and hippocampal atrophy, indistinguishable on
imaging from HS.170 It is unknown whether this imaging
evolution occurs in all patients with LE or it is specific to those
who present acute symptomatic seizures. According to some
studies, LE is the cause of 24% to 53% of TLE with HS (TLE-
HS) of adult onset. HS after LE is more often bilateral than
when related to other causes.165 LE must be considered in the
differential diagnosis of adults with recent TLE and amnesic
disturbances171 and thus should be investigated with brain MRI,
cerebrospinal fluid, search for occult neoplasia, and autoanti-
bodies related to LE. If the diagnosis is confirmed, long-term
immunotherapy (corticosteroids, IVIg, plasma exchange, cy-
clophosphamide, rituximab) is recommended, and in paraneo-
plastic cases, treating tumor is the priority.166
SUMMARY AND CONCLUSIONS
Severe head trauma, preeclampsia and possibly high-risk
SAH or ICH are so frequently related to seizures that pro-
phylaxis is recommended. A substantial proportion of in-
augural seizures (40%) are acute symptomatic. In this setting,
it is crucial to rapidly identify all insults possibly involved,
treat underlying diseases, reverse correctable factors, and, in
the case of CNS involvement, use AEDs during the acute
period. Risk of developing epilepsy is increased in patients
with neurological insults, mostly if accompanied with acute
symptomatic seizures, but not with metabolic disorders. Some
refractory epilepsies in adults, mostly epilepsy due to HS, may
be preceded by acute symptomatic seizures related to severe
insults including CNS infection, LE, head trauma, eclampsia,
and rarely RPL. New studies are needed in patients with acute
symptomatic seizures, taking each specific insult into consid-
eration separately, in order to better acknowledge risk factors
including the genetic ones involved in the development of
epilepsy. Hopefully, in the future “true” AEDs may be used in
this subgroup of patients to prevent the subsequent develop-
ment of epilepsy.
REFERENCES
1. Beghi E, Carpio A, Forsgren L, et al. Recommendation for
a definition of acute symptomatic seizure. Epilepsia. 2010;51:
671–675.
2. Guidelines for epidemiologic studies on epilepsy. Commission
on Epidemiology and Prognosis, International League Against
Epilepsy. Epilepsia. 1993;34:592–596.
3. Hauser WA, Annegers JF, Kurland LT. Prevalence of epilepsy in
Rochester, Minnesota: 1940-1980. Epilepsia. 1991;32:429–445.
4. Bauer G. Seizure types and epileptic syndromes in adults. Eur
Neurol. 1994;34(suppl 1):13–17.
5. Practice parameter: the neurodiagnostic evaluation of the child
with a first simple febrile seizure. American Academy of
Pediatrics. Provisional Committee on Quality Improvement,
Subcommittee on Febrile Seizures. Pediatrics. 1996;97:769–772;
discussion 773–775.
6. Scheffer IE, Berkovic SF. Generalized epilepsy with febrile
seizures plus. A genetic disorder with heterogeneous clinical
phenotypes. Brain. 1997;120(pt 3):479–490.
7. Engel J Jr. A proposed diagnostic scheme for people with
epileptic seizures and with epilepsy: report of the ILAE Task
Force on Classification and Terminology. Epilepsia. 2001;
42:796–803.
116 | www.theneurologist.org
The Neurologist  Volume 18, Number 3, May 2012
8. Delanty N, Vaughan CJ, French JA. Medical causes of seizures.
Lancet. 1998;352:383–390.
9. Hesdorffer DC, Benn EK, Cascino GD, et al. Is a first acute
symptomatic seizure epilepsy? Mortality and risk for recurrent
seizure. Epilepsia. 2009;50:1102–1108.
10. Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures
and epilepsy: definitions proposed by the International League
Against Epilepsy (ILAE) and the International Bureau for
Epilepsy (IBE). Epilepsia. 2005;46:470–472.
11. Fisher RS, Leppik I. Debate: when does a seizure imply epilepsy?
Epilepsia. 2008;49(suppl 9):7–12.
12. Hesdorffer DC, Logroscino G, Cascino G, et al. Risk of
unprovoked seizure after acute symptomatic seizure: effect of
status epilepticus. Ann Neurol. 1998;44:908–912.
13. Tardy B, Lafond P, Convers P, et al. Adult first generalized
seizure: etiology, biological tests, EEG, CT scan, in an ED. Am J
Emerg Med. 1995;13:1–5.
14. Dunn MJ, Breen DP, Davenport RJ, et al. Early management of
adults with an uncomplicated first generalised seizure. Emerg
Med J. 2005;22:237–242.
15. Krumholz A, Wiebe S, Gronseth G, et al. Practice parameter:
evaluating an apparent unprovoked first seizure in adults (an
evidence-based review): report of the Quality Standards Sub-
committee of the American Academy of Neurology and the
American Epilepsy Society. Neurology. 2007;69:1996–2007.
16. Wiebe S, Tellez-Zenteno JF, Shapiro M. An evidence-based
approach to the first seizure. Epilepsia. 2008;49(suppl 1):50–57.
17. Luders HO, Noachtar S. Atlas and Classification of Electro-
encephalography. Philadelphia: Saunders; 2000.
18. Temkin NR. Antiepileptogenesis and seizure prevention trials
with antiepileptic drugs: meta-analysis of controlled trials.
Epilepsia. 2001;42:515–524.
19. Butzkueven H, Evans AH, Pitman A, et al. Onset seizures
independently predict poor outcome after subarachnoid hemor-
rhage. Neurology. 2000;55:1315–1320.
20. Annegers JF, Hauser WA, Lee JR, et al. Incidence of acute
symptomatic seizures in Rochester, Minnesota, 1935-1984.
Epilepsia. 1995;36:327–333.
21. Loiseau J, Loiseau P, Guyot M, et al. Survey of seizure disorders
in the French southwest. I. Incidence of epileptic syndromes.
Epilepsia. 1990;31:391–396.
22. Costello DJ, Cole AJ. Treatment of acute seizures and status
epilepticus. J Intensive Care Med. 2007;22:319–347.
23. Faught E, Peters D, Bartolucci A, et al. Seizures after primary
intracerebral hemorrhage. Neurology. 1989;39:1089–1093.
24. Weisberg LA, Shamsnia M, Elliott D. Seizures caused by
nontraumatic parenchymal brain hemorrhages. Neurology. 1991;
41:1197–1199.
25. Bladin CF, Alexandrov AV, Bellavance A, et al. Seizures after
stroke: a prospective multicenter study. Arch Neurol. 2000;
57:1617–1622.
26. Ferro JM, Canhao P, Stam J, et al. Prognosis of cerebral vein and
dural sinus thrombosis: results of the International Study on
Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke.
2004;35:664–670.
27. Ferro JM, Correia M, Rosas MJ, et al. Seizures in cerebral vein
and dural sinus thrombosis. Cerebrovasc Dis. 2003;15:78–83.
28. Kim MA, Park KM, Kim SE, et al. Acute symptomatic seizures
in CNS infection. Eur J Neurol. 2008;15:38–41.
29. Bruns J Jr, Hauser WA. The epidemiology of traumatic brain
injury: a review. Epilepsia. 2003;44(suppl 10):2–10.
30. Starkey IR, Lawson AA. Psychiatric aspects of acute poisoning
with tricyclic and related antidepressants—a ten-year review.
Scott Med J. 1980;25:303–308.
31. Devinsky O, Honigfeld G, Patin J. Clozapine-related seizures.
Neurology. 1991;41:369–371.
32. Pascual-Leone A, Dhuna A, Altafullah I, et al. Cocaine-induced
seizures. Neurology. 1990;40(pt 1):404–407.
33. Dhuna A, Pascual-Leone A, Langendorf F, et al. Epileptogenic
properties of cocaine in humans. Neurotoxicology. 1991;12:621–626.
34. Alldredge BK, Lowenstein DH, Simon RP. Seizures associated
with recreational drug abuse. Neurology. 1989;39:1037–1039.
r 2012 Lippincott Williams & Wilkins
The Neurologist  Volume 18, Number 3, May 2012
35. Boggs JG. Seizures in medically complex patients. Epilepsia.
1997;38(suppl 4):S55–S59.
36. Whang R, Hampton EM, Whang DD. Magnesium homeostasis
and clinical disorders of magnesium deficiency. Ann Pharmac-
other. 1994;28:220–226.
37. Gao X, Wee AS, Nick TG. Effect of keto-acidosis on seizure
occurrence in diabetic patients. J Miss State Med Assoc.
2005;46:131–133.
38. Lamy C, Domigo V, Semah F, et al. Early and late seizures after
cryptogenic ischemic stroke in young adults. Neurology.
2003;60:400–404.
39. Beghi E, D’Alessandro R, Beretta S, et al. Incidence and
predictors of acute symptomatic seizures after stroke. Neurology.
2011;77:1785–1793.
40. Sung CY, Chu NS. Epileptic seizures in thrombotic stroke.
J Neurol. 1990;237:166–170.
41. Kelly KM. Animal modeling of poststroke seizures and epilepsy:
5-year update. Epilepsy Curr. 2007;7:159–162.
42. Labovitz DL, Hauser WA, Sacco RL. Prevalence and predictors
of early seizure and status epilepticus after first stroke.
Neurology. 2001;57:200–206.
43. Hijdra A, Brouwers PJ, Vermeulen M, et al. Grading the amount
of blood on computed tomograms after subarachnoid hemor-
rhage. Stroke. 1990;21:1156–1161.
44. Arboix A, Garcia-Eroles L, Massons JB, et al. Predictive factors
of early seizures after acute cerebrovascular disease. Stroke.
1997;28:1590–1594.
45. Qureshi AI, Sung GY, Suri MA, et al. Prognostic value and
determinants of ultraearly angiographic vasospasm after
aneurysmal subarachnoid hemorrhage. Neurosurgery. 1999;44:
967–973; discussion 973–964.
46. Noachtar S, Peters AS. Semiology of epileptic seizures: a critical
review. Epilepsy Behav. 2009;15:2–9.
47. Gilmore E, Choi HA, Hirsch LJ, et al. Seizures and CNS
hemorrhage: spontaneous intracerebral and aneurysmal subar-
achnoid hemorrhage. Neurologist. 2010;16:165–175.
48. Bederson JB, Connolly ES, Batjer HH, et al. Guidelines for the
management of aneurysmal subarachnoid hemorrhage: a state-
ment for healthcare professionals from a special writing group
of the Stroke Council, American Heart Association. Stroke.
2009;40:994–1025.
49. Naidech AM, Kreiter KT, Janjua N, et al. Phenytoin exposure is
associated with functional and cognitive disability after sub-
arachnoid hemorrhage. Stroke. 2005;36:583–587.
50. Hasan D, Schonck RS, Avezaat CJ, et al. Epileptic seizures after
subarachnoid hemorrhage. Ann Neurol. 1993;33:286–291.
51. Herman ST. Epilepsy after brain insult: targeting epileptogenesis.
Neurology. 2002;59(suppl 5):S21–S26.
52. De Herdt V, Dumont F, Henon H, et al. Early seizures in
intracerebral hemorrhage: incidence, associated factors, and
outcome. Neurology. 2011;77:1794–1800.
53. Kucukkaya B, Aker R, Yuksel M, et al. Low dose MK-801
protects against iron-induced oxidative changes in a rat model of
focal epilepsy. Brain Res. 1998;788:133–136.
54. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the
management of spontaneous intracerebral hemorrhage in adults:
2007 update: a guideline from the American Heart Association/
American Stroke Association Stroke Council, High Blood
Pressure Research Council, and the Quality of Care and
Outcomes in Research Interdisciplinary Working Group. Stroke.
2007;38:2001–2023.
55. Passero S, Rocchi R, Rossi S, et al. Seizures after spontaneous
supratentorial intracerebral hemorrhage. Epilepsia. 2002;43:
1175–1180.
56. Kilpatrick CJ, Davis SM, Tress BM, et al. Epileptic seizures in
acute stroke. Arch Neurol. 1990;47:157–160.
57. Schulz UG, Rothwell PM. Transient ischaemic attacks mimick-
ing focal motor seizures. Postgrad Med J. 2002;78:246–247.
58. Noachtar S. Seizure semiology. In: Lüders HO, ed. Epilepsy:
Comprehensive Review and Case Discussions. London: Martin
Dunitz Publishers; 2001:127–140.
r 2012 Lippincott Williams & Wilkins
Acute Symptomatic Seizures: A Review
59. Giroud M, Dumas R. Role of associated cortical lesions in motor
partial seizures and lenticulostriate infarcts. Epilepsia. 1995;36:
465–470.
60. Kammersgaard LP, Olsen TS. Poststroke epilepsy in the
Copenhagen stroke study: incidence and predictors. J Stroke
Cerebrovasc Dis. 2005;14:210–214.
61. Sun DA, Sombati S, DeLorenzo RJ. Glutamate injury-induced
epileptogenesis in hippocampal neurons: an in vitro model of
stroke-induced “epilepsy”. Stroke. 2001;32:2344–2350.
62. Guidelines for management of ischaemic stroke and transient
ischaemic attack 2008. Cerebrovasc Dis. 2008;25:
457–507.
63. De Reuck J, De Groote L, Van Maele G. Single seizure and
epilepsy in patients with a cerebral territorial infarct. J Neurol
Sci. 2008;271:127–130.
64. Ryvlin P, Montavont A, Nighoghossian N. Optimizing therapy of
seizures in stroke patients. Neurology. 2006;67(suppl 4):S3–S9.
65. Zemke D, Farooq MU, Gupta R, et al. The effect of
anticonvulsant drugs on the fibrinolytic activity of tissue
plasminogen activator. Cerebrovasc Dis. 2008;25:107–110.
66. Rodan LH, Aviv RI, Sahlas DJ, et al. Seizures during stroke
thrombolysis heralding dramatic neurologic recovery. Neurology.
2006;67:2048–2049.
67. Fleitman JS, Bruni J, Perrin JH, et al. Albumin-binding
interactions of sodium valproate. J Clin Pharmacol. 1980;20:
514–517.
68. Glauser T, Ben-Menachem E, Bourgeois B, et al. ILAE treatment
guidelines: evidence-based analysis of antiepileptic drug efficacy
and effectiveness as initial monotherapy for epileptic seizures
and syndromes. Epilepsia. 2006;47:1094–1120.
69. Alvarez-Sabin J, Montaner J, Padro L, et al. Gabapentin in late-
onset poststroke seizures. Neurology. 2002;59:1991–1993.
70. Reith J, Jorgensen HS, Nakayama H, et al. Seizures in acute
stroke: predictors and prognostic significance. The Copenhagen
Stroke Study. Stroke. 1997;28:1585–1589.
71. Williams AJ, Tortella FC. Neuroprotective effects of the sodium
channel blocker RS100642 and attenuation of ischemia-induced
brain seizures in the rat. Brain Res. 2002;932:45–55.
72. Ferro JM, Canhao P, Bousser MG, et al. Early seizures in
cerebral vein and dural sinus thrombosis: risk factors and role of
antiepileptics. Stroke. 2008;39:1152–1158.
73. Kwan J, Guenther A. Antiepileptic drugs for the primary and
secondary prevention of seizures after intracranial venous
thrombosis. Cochrane Database Syst Rev. 2006;3:CD005501.
74. Annegers JF, Grabow JD, Groover RV, et al. Seizures after head
trauma: a population study. Neurology. 1980;30(pt 1):683–689.
75. Temkin NR, Dikmen SS, Wilensky AJ, et al. A randomized,
double-blind study of phenytoin for the prevention of post-
traumatic seizures. N Engl J Med. 1990;323:497–502.
76. Chang BS, Lowenstein DH. Practice parameter: antiepileptic
drug prophylaxis in severe traumatic brain injury: report of the
Quality Standards Subcommittee of the American Academy of
Neurology. Neurology. 2003;60:10–16.
77. Beghi E. Overview of studies to prevent posttraumatic epilepsy.
Epilepsia. 2003;44(suppl 10):21–26.
78. Glotzner FL, Haubitz I, Miltner F, et al. Seizure prevention using
carbamazepine following severe brain injuries. Neurochirurgia
(Stuttg). 1983;26:66–79.
79. Temkin NR, Dikmen SS, Anderson GD, et al. Valproate therapy
for prevention of posttraumatic seizures: a randomized trial.
J Neurosurg. 1999;91:593–600.
80. Annegers JF, Hauser WA, Coan SP, et al. A population-based
study of seizures after traumatic brain injuries. N Engl J Med.
1998;338:20–24.
81. Annegers JF, Hauser WA, Beghi E, et al. The risk of unprovoked
seizures after encephalitis and meningitis. Neurology. 1988;38:
1407–1410.
82. Diaz-Arrastia R, Agostini MA, Frol AB, et al. Neurophysiologic
and neuroradiologic features of intractable epilepsy after
traumatic brain injury in adults. Arch Neurol. 2000;57:
1611–1616.
www.theneurologist.org | 117
Beleza
83. Temkin NR. Preventing and treating posttraumatic seizures: the
human experience. Epilepsia. 2009;50(suppl 2):10–13.
84. Cornejo BJ, Mesches MH, Coultrap S, et al. A single episode of
neonatal seizures permanently alters glutamatergic synapses. Ann
Neurol. 2007;61:411–426.
85. Rakhade SN, Zhou C, Aujla PK, et al. Early alterations of AMPA
receptors mediate synaptic potentiation induced by neonatal
seizures. J Neurosci. 2008;28:7979–7990.
86. McNamara JO, Huang YZ, Leonard AS. Molecular signaling
mechanisms underlying epileptogenesis. Sci STKE. 2006;
2006:re12.
87. Vezzani A, Granata T. Brain inflammation in epilepsy:
experimental and clinical evidence. Epilepsia. 2005;46:
1724–1743.
88. Scharfman HE. The neurobiology of epilepsy. Curr Neurol
Neurosci Rep. 2007;7:348–354.
89. Dudek FE, Sutula TP. Epileptogenesis in the dentate gyrus: a
critical perspective. Prog Brain Res. 2007;163:755–773.
90. Pitkanen A, Immonen RJ, Grohn OH, et al. From traumatic brain
injury to posttraumatic epilepsy: what animal models tell us
about the process and treatment options. Epilepsia. 2009;
50(suppl 2):21–29.
91. Jensen FE. Introduction. Posttraumatic epilepsy: treatable
epileptogenesis. Epilepsia. 2009;50(suppl 2):1–3.
92. Misra UK, Tan CT, Kalita J. Viral encephalitis and epilepsy.
Epilepsia. 2008;49(suppl 6):13–18.
93. Beghi E, Carpio A, Forsgren L, et al. Recommendation for a
definition of acute symptomatic seizure. Epilepsia. 2010;51:
671–675.
94. Nash TE, Del Brutto OH, Butman JA, et al. Calcific neuro-
cysticercosis and epileptogenesis. Neurology. 2004;62:1934–
1938.
95. Wang S, Cheng Q, Malik S, et al. Interleukin-1beta inhibits
gamma-aminobutyric acid type A (GABA(A)) receptor current in
cultured hippocampal neurons. J Pharmacol Exp Ther. 2000;
292:497–504.
96. Carpio A, Hauser WA. Prognosis for seizure recurrence in
patients with newly diagnosed neurocysticercosis. Neurology.
2002;59:1730–1734.
97. Medina MT, Rosas E, Rubio-Donnadieu F, et al. Neuro-
cysticercosis as the main cause of late-onset epilepsy in Mexico.
Arch Intern Med. 1990;150:325–327.
98. Trinka E, Dubeau F, Andermann F, et al. Successful epilepsy
surgery in catastrophic postencephalitic epilepsy. Neurology.
2000;54:2170–2173.
99. Marks DA, Kim J, Spencer DD, et al. Characteristics of
intractable seizures following meningitis and encephalitis.
Neurology. 1992;42:1513–1518.
100. O’Brien TJ, Moses H, Cambier D, et al. Age of meningitis or
encephalitis is independently predictive of outcome from anterior
temporal lobectomy. Neurology. 2002;58:104–109.
101. Schlitt M, Bucher AP, Quindlen EA, et al. Nonfulminant herpes
simplex encephalitis as a cause for mesial temporal sclerosis.
Med Hypotheses. 1990;33:177–179.
102. Theodore WH, Epstein L, Gaillard WD, et al. Human herpes
virus 6B: a possible role in epilepsy? Epilepsia. 2008;49:
1828–1837.
103. Gutnick MJ, Van Duijn H, Citri N. Relative convulsant potencies
of structural analogues of penicillin. Brain Res. 1976;114:139–
143.
104. Fujimoto M, Munakata M, Akaike N. Dual mechanisms of
GABAA response inhibition by beta-lactam antibiotics in the
pyramidal neurones of the rat cerebral cortex. Br J Pharmacol.
1995;116:3014–3020.
105. Morrow LE, Wear RE, Schuller D, et al. Acute isoniazid toxicity
and the need for adequate pyridoxine supplies. Pharmacotherapy.
2006;26:1529–1532.
106. Montgomery SA. Antidepressants and seizures: emphasis on
newer agents and clinical implications. Int J Clin Pract.
2005;59:1435–1440.
107. Brust JC. Seizures and substance abuse: treatment considerations.
Neurology. 2006;67(suppl 4):S45–S48.
118 | www.theneurologist.org
The Neurologist  Volume 18, Number 3, May 2012
108. Cubala WJ, Landowski J. Seizure following sudden zolpidem
withdrawal. Prog Neuropsychopharmacol Biol Psychiatry.
2007;31:539–540.
109. Fialip J, Aumaitre O, Eschalier A, et al. Benzodiazepine
withdrawal seizures: analysis of 48 case reports. Clin Neuro-
pharmacol. 1987;10:538–544.
110. Fraser HF, Wikler A, Essig CF, et al. Degree of physical
dependence induced by secobarbital or pentobarbital. J Am Med
Assoc. 1958;166:126–129.
111. Sellers EM. Alcohol, barbiturate and benzodiazepine withdrawal
syndromes: clinical management. CMAJ. 1988;139:113–120.
112. Martinez-Cano H, Vela-Bueno A, de Iceta M, et al. Benzodia-
zepine withdrawal syndrome seizures. Pharmacopsychiatry.
1995;28:257–262.
113. Denis C, Fatseas M, Lavie E, et al. Pharmacological interventions
for benzodiazepine mono-dependence management in outpatient
settings. Cochrane Database Syst Rev. 2006;3:CD005194.
114. Wijdicks EF, Sharbrough FW. New-onset seizures in critically ill
patients. Neurology. 1993;43:1042–1044.
115. Earnest MP, Yarnell PR. Seizure admissions to a city hospital:
the role of alcohol. Epilepsia. 1976;17:387–393.
116. Rathlev NK, Ulrich A, Shieh TC, et al. Etiology and weekly
occurrence of alcohol-related seizures. Acad Emerg Med.
2002;9:824–828.
117. Sand T, Brathen G, Michler R, et al. Clinical utility of EEG in
alcohol-related seizures. Acta Neurol Scand. 2002;105:18–24.
118. McKeon A, Frye MA, Delanty N. The alcohol withdrawal
syndrome. J Neurol Neurosurg Psychiatry. 2008;79:854–862.
119. Faingold CL, Riaz A. Ethanol withdrawal induces increased
firing in inferior colliculus neurons associated with audiogenic
seizure susceptibility. Exp Neurol. 1995;132:91–98.
120. Feng HJ, Yang L, Faingold CL. Role of the amygdala in ethanol
withdrawal seizures. Brain Res. 2007;1141:65–73.
121. Hillbom M, Pieninkeroinen I, Leone M. Seizures in alcohol-
dependent patients: epidemiology, pathophysiology and manage-
ment. CNS Drugs. 2003;17:1013–1030.
122. Rathlev NK, Ulrich A. Clinical characteristics as predictors of
recurrent alcohol-related seizures. Acad Emerg Med. 2000;
7:886–891.
123. Brathen G, Ben-Menachem E, Brodtkorb E, et al. EFNS
guideline on the diagnosis and management of alcohol-related
seizures: report of an EFNS task force. Eur J Neurol.
2005;12:575–581.
124. Hughes JR. Alcohol withdrawal seizures. Epilepsy Behav.
2009;15:92–97.
125. Alcohol withdrawal syndrome: how to predict, prevent, diagnose
and treat it. Prescrire Int. 2007;16:24–31.
126. Abraham HD, Duffy FH. EEG coherence in post-LSD visual
hallucinations. Psychiatry Res. 2001;107:151–163.
127. Fisher DD, Ungerleider JT. Grand mal seizures following
ingestion of LSD. Calif Med. 1967;106:210–211.
128. Brust J. Seizures and illicit drug use. In: Delanty N, ed. Seizures:
medical causes and management. Totowa, NJ: Humana Press,
Inc; 2001:183–192.
129. Ng SK, Brust JC, Hauser WA, et al. Illicit drug use and the risk of
new-onset seizures. Am J Epidemiol. 1990;132:47–57.
130. Riggs JE. Neurologic manifestations of electrolyte disturbances.
Neurol Clin. 2002;20:227–239. vii.
131. Kahn A, Blum D, Casimir G, et al. Controlled fall in natremia in
hypertonic dehydration: possible avoidance of rehydration
seizures. Eur J Pediatr. 1981;135:293–296.
132. Kunze K. Metabolic encephalopathies. J Neurol. 2002;249:
1150–1159.
133. Krumholz A, Stern BJ, Weiss HD. Outcome from coma after
cardiopulmonary resuscitation: relation to seizures and myoclo-
nus. Neurology. 1988;38:401–405.
134. Wijdicks EF, Parisi JE, Sharbrough FW. Prognostic value of
myoclonus status in comatose survivors of cardiac arrest. Ann
Neurol. 1994;35:239–243.
135. Zandbergen EG, Hijdra A, Koelman JH, et al. Prediction of poor
outcome within the first 3 days of postanoxic coma. Neurology.
2006;66:62–68.
r 2012 Lippincott Williams & Wilkins
The Neurologist  Volume 18, Number 3, May 2012
136. Wijdicks EF, Hijdra A, Young GB, et al. Practice parameter:
prediction of outcome in comatose survivors after cardiopulmo-
nary resuscitation (an evidence-based review): report of the
Quality Standards Subcommittee of the American Academy of
Neurology. Neurology. 2006;67:203–210.
137. Morris HR, Howard RS, Brown P. Early myoclonic status and
outcome after cardiorespiratory arrest. J Neurol Neurosurg
Psychiatry. 1998;64:267–268.
138. Arnoldus EP, Lammers GJ. Postanoxic coma: good recovery
despite myoclonus status. Ann Neurol. 1995;38:697–698.
139. Werhahn KJ, Brown P, Thompson PD, et al. The clinical features
and prognosis of chronic posthypoxic myoclonus. Mov Disord.
1997;12:216–220.
140. Harper SJ, Wilkes RG. Posthypoxic myoclonus (the Lance-
Adams syndrome) in the intensive care unit. Anaesthesia.
1991;46:199–201.
141. Bass E. Cardiopulmonary arrest. Pathophysiology and neurologic
complications. Ann Intern Med. 1985;103(pt 1):920–927.
142. Rossetti AO, Oddo M, Liaudet L, et al. Predictors of awakening
from postanoxic status epilepticus after therapeutic hypothermia.
Neurology. 2009;72:744–749.
143. Caviness JN, Brown P. Myoclonus: current concepts and recent
advances. Lancet Neurol. 2004;3:598–607.
144. Young GB, Jordan KG, Doig GS. An assessment of non-
convulsive seizures in the intensive care unit using continuous
EEG monitoring: an investigation of variables associated with
mortality. Neurology. 1996;47:83–89.
145. Kaplan PW. EEG criteria for nonconvulsive status epilepticus.
Epilepsia. 2007;48(suppl 8):39–41.
146. Bauer G, Trinka E. Nonconvulsive status epilepticus and coma.
Epilepsia. 2010;51:177–190.
147. Brenner RP. Is it status? Epilepsia. 2002;43(suppl 3):103–113.
148. Waterhouse EJ, Vaughan JK, Barnes TY, et al. Synergistic effect
of status epilepticus and ischemic brain injury on mortality.
Epilepsy Res. 1998;29:175–183.
149. Drislane FW, Schomer DL. Clinical implications of generalized
electrographic status epilepticus. Epilepsy Res. 1994;19:111–121.
150. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet.
2005;365:785–799.
151. Sibai BM, El-Nazer A, Gonzalez-Ruiz A. Severe preeclampsia-
eclampsia in young primigravid women: subsequent pregnancy
outcome and remote prognosis. Am J Obstet Gynecol. 1986;155:
1011–1016.
152. Shah AK, Rajamani K, Whitty JE. Eclampsia: a neurological
perspective. J Neurol Sci. 2008;271:158–167.
153. Douglas KA, Redman CW. Eclampsia in the United Kingdom.
BMJ. 1994;309:1395–1400.
154. Loureiro R, Leite CC, Kahhale S, et al. Diffusion imaging may
predict reversible brain lesions in eclampsia and severe
r 2012 Lippincott Williams & Wilkins
Acute Symptomatic Seizures: A Review
preeclampsia: initial experience. Am J Obstet Gynecol. 2003;
189:1350–1355.
155. Wasseff S. Mechanisms of convulsions in eclampsia. Med
Hypotheses. 2009;72:49–51.
156. Altman D, Carroli G, Duley L, et al. Do women with pre-
eclampsia, and their babies, benefit from magnesium sulphate?
The Magpie Trial: a randomised placebo-controlled trial. Lancet.
2002;359:1877–1890.
157. Which anticonvulsant for women with eclampsia? Evidence from
the Collaborative Eclampsia Trial. Lancet. 1995;345:1455–1463.
158. Euser AG, Cipolla MJ. Magnesium sulfate for the treatment of
eclampsia: a brief review. Stroke. 2009;40:1169–1175.
159. Wu CS, Sun Y, Vestergaard M, et al. Preeclampsia and risk for
epilepsy in offspring. Pediatrics. 2008;122:1072–1078.
160. Lawn N, Laich E, Ho S, et al. Eclampsia, hippocampal sclerosis,
and temporal lobe epilepsy: accident or association? Neurology.
2004;62:1352–1356.
161. Lee VH, Wijdicks EF, Manno EM, et al. Clinical spectrum of
reversible posterior leukoencephalopathy syndrome. Arch Neu-
rol. 2008;65:205–210.
162. Bakshi R, Bates VE, Mechtler LL, et al. Occipital lobe seizures
as the major clinical manifestation of reversible posterior
leukoencephalopathy syndrome: magnetic resonance imaging
findings. Epilepsia. 1998;39:295–299.
163. Schwartz RB. A reversible posterior leukoencephalopathy
syndrome. N Engl J Med. 1996;334:1743; author reply 1746.
164. Solinas C, Briellmann RS, Harvey AS, et al. Hypertensive
encephalopathy: antecedent to hippocampal sclerosis and tem-
poral lobe epilepsy? Neurology. 2003;60:1534–1536.
165. Bien CG, Elger CE. Limbic encephalitis: a cause of temporal
lobe epilepsy with onset in adult life. Epilepsy Behav.
2007;10:529–538.
166. Tuzun E, Dalmau J. Limbic encephalitis and variants: classi-
fication, diagnosis and treatment. Neurologist. 2007;13:261–271.
167. Vincent A, Buckley C, Schott JM, et al. Potassium channel
antibody-associated encephalopathy: a potentially immunotherapy-
responsive form of limbic encephalitis. Brain. 2004;127:701–712.
168. Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive
limbic encephalitis identified by neuropil antibodies: MRI and
PET correlates. Brain. 2005;128:1764–1777.
169. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic
encephalitis: neurological symptoms, immunological findings
and tumour association in 50 patients. Brain. 2000;123(Pt 7):
1481–1494.
170. Urbach H, Soeder BM, Jeub M, et al. Serial MRI of limbic
encephalitis. Neuroradiology. 2006;48:380–386.
171. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and
unprovoked seizures in Rochester, Minnesota: 1935-1984.
Epilepsia. 1993;34:453–468.
www.theneurologist.org | 119