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▶ Appendix 1 is published
online only. To view this file
please visit the journal online
(http://pn.bmj.com/content/12/3.
toc).
1
Department of Neurology,
Morriston Hospital, Swansea, UK
2
Department of Neurology,
University Hospital of Wales,
Cardiff, UK
Correspondence to
Rob Powell, Morriston
Hospital, Department of
Neurology, Heol Maes Eglwys,
Swansea SA6 6NL, UK;
robpowell@doctors.org.uk
154 Practical Neurology 2012;12:154–165. doi:10.1136/practneurol-2012-000244
Acute symptomatic seizures
Rob Powell,1 Duncan James McLauchlan2
Abstract
Acute symptomatic seizures occur in close
temporal proximity to a documented neurological
or systemic insult. They are a common reason
for seeking an emergency neurological
opinion. We discuss their important causes,
treatment and prognosis, discuss a practical
approach to their clinical assessment and
investigation, and offer thoughts on treatment.
Introduction
Acute symptomatic seizures are defined as
clinical seizures occurring at the time of, or
in close temporal relationship with, a doc-
umented central nervous system (CNS) or
systemic insult, which may be metabolic,
toxic, structural, infectious or inflammato-
ry.1 They differ from unprovoked seizures
in terms of underlying aetiology, investiga-
tions, treatment and should be separately
categorised for epidemiologic purposes.
The risk of seizure recurrence following an
acute symptomatic seizure depends on the
underlying aetiology, but in general is sig-
nificantly lower than that following a sin-
gle unprovoked seizure. Some neurologists
prefer to view acute symptomatic seizures
as a result of interacting factors including
genetic predisposition, structural lesions
and provoking insult. The term ‘provoked
seizures’ is sometimes used, including in
the Driver and Vehicle Licensing Agency
(DVLA) guidelines; however, this can lead
to confusion with, for example, seizures in
idiopathic generalised epilepsy provoked
by sleep deprivation.
Acute symptomatic seizures are a common
reason for medical admission and require
thoughtful investigation. We review their
clinical presentation in adults (box 1,
table 1), their important causes and appro-
priate investigations (box 2, table 1), and
their treatment and prognosis (box 3).
Although childhood febrile convulsions
are, by definition, acute symptomatic sei-
zures, they are not covered here.
Aetiology
The term acute symptomatic seizures spe-
cifically imply seizures occurring at the
time of the initial illness, which do not
recur, and in general do not require long
term treatment with antiepileptic medica-
tion. The conditions listed below can cause
either complex partial or tonic-clonic sei-
zures, and may present with status epi-
lepticus. They may also cause recurring,
unprovoked seizures, that is, epilepsy, as
well as acute symptomatic seizures. The
occurrence of acute symptomatic seizures
increases the risks of future unprovoked
seizures, in some instances.
Cerebrovascular disease
Arterial infarction
Stroke causes both acute symptomatic
seizures and epilepsy. Recent studies
have suggested 2.5%–5.0% of patients
develop early seizures and these suggest
a worse prognosis.2 3 The seizure risk is
higher with larger infarctions, especially
if involving the cortex; seizures are less
copyright.
likely with deep white matter ischaemic
lesions. Acute symptomatic seizures in
stroke do not consistently influence the
outcome or the risk of subsequent post-
stroke epilepsy.2 A seizure at stroke onset
is a relative contraindication to thrombol-
ysis, and is more suggestive of other diag-
noses, such as venous sinus thrombosis or
intracerebral haemorrhage.
Venous infarction
Cerebral venous sinus thrombosis is an
uncommon cause of cortical infarction
and intracerebral haemorrhage (figure 1).
It is slightly more common in women than
in men. It presents with headache (either
non-specific or with raised pressure fea-
tures), encephalopathy, focal neurological
symptoms or seizures, and there may be
papilloedema. Seizures may be difficult
to control. As yet, there is no evidence to
support or refute using antiepileptic drugs
(AEDs) for the primary or secondary pre-
vention of seizures following cerebral
venous sinus thrombosis;4 however, we
discuss our own practice later.
Intracranial haemorrhage
The risk of acute symptomatic seizures
is higher with intracerebral haemorrhage
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Box 1 Important clinical features

1. History
A detailed history is crucial in establishing the underlying cause. Important points to consider in the history include:
a. Event description
A witness account is extremely valuable and should always be sought. This may provide information about the location of seizure
onset and help to distinguish seizures from other causes of transient loss of consciousness, for example, syncope and psychogenic
non-epileptic attacks. Examples of conditions easily mistaken for seizures include rigors in the acutely unwell febrile patient, panic at-
tacks, shaking limb transient ischaemic attacks, sudden reduced vigilance following thalamic infarcts and dyskinesias in anti-n-methyl
d-aspartate encephalitis.
b. Associated neurological features
These are important in distinguishing from unprovoked seizures and in guiding further investigations:
■ Headache, which may be severe or relatively non-specific. It may be present in intracranial haemorrhage, venous thrombosis, space

occupying lesion, infective and inflammatory disorders

■ Meningism features, for example, fever, photophobia, neck stiffness

■ Altered consciousness

■ Head trauma: minor head trauma may lead to subdural haematoma particularly in the older people, those on anticoagulants or anti-

platelets and people who are heavy consumers of alcohol

■ Focal neurological symptoms

■ Myoclonus, dystonia or other movement disorders

c. Speed of onset of any prodromal symptoms

Although the seizures are of sudden onset (by definition), the tempo of preceding symptoms may point to the underlying aetiology.
Abrupt onset implies a vascular or traumatic event; symptoms evolving over days to weeks imply an infective or inflammatory pathology;
evolution over weeks or months suggests a space-occupying lesion.
d. Other points
■ Intercurrent illness or infection

■ Foreign travel and sexually transmitted infection history

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■ Alcohol intake, illicit drug use

■ Concomitant medication including ‘over-the-counter’ medication

■ Relevant past medical history including malignancy, stroke, diabetes mellitus, recent surgery, systemic inflammatory conditions, car-

diovascular and respiratory disease and metabolic disorders

2. Examination
a. General
■ Temperature, blood pressure, plasma glucose

■ Skin: for purpuric or vasculitic rash, or features suggesting a neurocutaneous disorder

■ Joints: for evidence of arthropathy

■ Cardiovascular: for example, heart murmurs

■ Chest and abdomen: for evidence of sepsis (consolidation or abdominal tenderness)

b. Neurological
■ Reduced level of consciousness or impaired alertness may reflect a postictal state or may imply significant intracranial pathology
■ Signs of raised intracranial pressure, such as dilated pupil, sixth nerve palsy, papilloedema

■ Meningism, for example, neck stiffness, photophobia, Kernig’s and Brudzinski’s signs

■ Focal neurological signs

■ Evidence of ongoing seizure activity, for example, myoclonus, focal twitching, fluctuating conscious level, nystagmus

than with ischaemic stroke; occurring in 16% of
patients in a recent study.3 It is greatest following haem-
orrhage into frontal, temporal and parietal lobes, and
is less when involving the deep white matter or occipi-
tal lobes. Haemorrhage secondary to a vascular mal-
formation (cavernoma or arteriovenous malformation)
carries a higher seizure risk than spontaneous haemor-
rhage or haemorrhage secondary to hypertension.5
Subarachnoid haemorrhage from aneurysmal rup-
ture carries a 10% risk of seizure; most occur at the
onset. Early onset of seizures carries a poor prognosis.
In one study, 7% of patients subsequently developed
epilepsy, the risk increasing with ischaemia and large
subdural collections.6
Hypertensive encephalopathy and the posterior
reversible encephalopathy syndrome
Posterior reversible encephalopathy syndrome is a
clinico-radiological diagnosis. It most commonly
occurs with hypertension and previously was known
as hypertensive encephalopathy. There are several
other aetiological factors, including renal disease,

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Figure 1 CT scan of head showing transverse sinus thrombosis causing venous infarctions and haemorrhagic transformation with
intracerebral and subarachnoid haemorrhage.
immunosuppression, organ transplantation, eclamp-
sia, autoimmune disease and infection. The underlying
pathophysiology is unclear: the several proposed theo-
ries include altered blood–brain barrier due to break-
down in cerebral autoregulation, focal vasospasm and
endothelial dysfunction. Common clinical features are
headache, altered mentation, seizures and visual distur-
bance. Characteristic MR brain scan changes develop
in the parietal and occipital lobes (figure 2). The man-
agement is to treat any underlying disorder and to treat
blood pressure aggressively, with intravenous agents if
necessary. The limited evidence suggests that long term
antiepileptic therapy is not usually required.7
Infection
Meningitis
Seizures complicate the acute stage of bacterial menin-
gitis in 17%–24% of cases; these patients have a higher
mortality.8 9 Seizures tend to occur early in the disease
and are significantly more likely in patients with tachy-
cardia, low Glasgow coma score, Streptococcus pneu-
moniae infection and focal neurological abnormalities.8
Bacterial meningitis in adults is most commonly caused
by S pneumoniae and Neisseria meningitis. The long
term risk of developing epilepsy (overall 2.7%) has been
shown to be higher in those who experience acute symp-
tomatic seizures (8%) than in those without (1.6%).9
Tuberculous meningitis has a subacute and subtle onset;
patients may be withdrawn or have subtle personal-
ity change as well as having the slow onset of menin-
geal features. With progression of the disease, patients
become more obtunded and develop focal neurological
signs. Seizures can result from tuberculomata within
the cortex from direct spread of the infection.
Viral encephalitis
Encephalitis presents indolently with headache, altered
mental status and personality change. Meningism and
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fever may also occur. Herpes simplex virus encephalitis
has a predilection for the temporal lobes; temporal lobe
seizures develop in a quarter of cases (figure 3). Treatment
depends upon identifying the causative agent from serol-
ogy or CSF. Most patients are started on acyclovir, as
this has broad spectrum activity against the commoner
infecting organisms. The risk of subsequently develop-
copyright.
ing unprovoked seizures is significantly increased fol-
lowing viral encephalitis, particularly if accompanied by
acute symptomatic seizures, with epilepsy rates of over
20%.10
Endocarditis
A minority of patients with infective endocarditis
develop seizures. These may result from infective
emboli causing infarction, abscess or meningitis or may
be due to the systemic consequences of infection (elec-
trolyte derangement, renal failure and septicaemia).
Cerebral abscess
Abscesses are more common in the developing world
and may be a consequence of local invasion or distant
haematogenous spread (figure 4). Risk factors include
ear, nose and throat infections, penetrating injuries
from head trauma or neurosurgical procedures, diabe-
tes mellitus, immunocompromise and congenital heart
disease. Cerebral abscess commonly presents with
headache, focal neurology, fever and signs of raised
intracranial pressure. A recent large retrospective study
found a lower rate of seizures than previously thought,
with 17% developing acute symptomatic seizures.11
Generally, prophylactic AEDs were not used. Of the
patients with seizures, 27% were continued on AEDs
after resolution of the acute event and had no further
seizures, whilst 19% developed epilepsy.
Tropical diseases
Neurocysticercosis is among the most common causes
of epilepsy in the developing world, but may also
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Figure 2 Axial FLAIR MRI images showing bi-parietal hyperintensities in a patient with posterior reversible encephalopathy syndrome.

Figure 3 Axial T2 weighted (left) and FLAIR (right) MRI revealing bilateral temporal lobe high signal in viral encephalitis. copyright.

present with acute symptomatic seizures in the con-
text of the brain’s inflammatory response to infection.
The tapeworm parasite Taenia solium crosses into the
bloodstream from the gastrointestinal tract and may
seed in the CNS (figure 5). There is mixed evidence
for clinical improvement following treatment with
praziquantel and corticosteroids.12 Schistosomiasis can
cause an encephalopathic presentation with general-
ised seizures or seeding of ova in the brain may lead to
partial-onset seizures.
Malaria is extremely common in the developing world.
The cerebral form predominantly affects children and
young adults. The infected erythrocytes occlude cerebral
capillaries and may trigger a vasculitic reaction. The pri-
mary presentation is with acute encephalitis, leading to
generalised seizures in 40% of adults. Focal neurologi-
cal signs may develop but tend not to persist. Treatment
takes account of the international guidelines from the
WHO and is adapted for local resistance patterns.
HIV
Early studies, before widespread use of highly active
antiretroviral therapy, gave a seizure prevalence of
11%–17%.13 Later studies showed a disparity in preva-
lence between treatment naïve (19.8%)14 and those with
access to antiviral therapy (6%).15 These figures refer to

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Figure 4 Axial T2 weighted MRI image demonstrating a
cerebral abscess with typical surrounding oedema.

both epilepsy and acute symptomatic seizures, which

may occur in the context of direct HIV cerebral infec-
tion, protozoal infections, (for example, Toxoplasma
gondii causing mass lesions), cryptococcal meningitis,
cerebral tuberculosis or other atypical infections. Figure 5 Axial T1 weighted MRI showing multiple cystic
lesions in a patient with neurocysticercosis.
Head injury

The risk of seizures increases after head injury, and
depends upon the injury severity and the intracranial
sequelae (figure 6). Head injury is categorised as mild
(<30 min amnesia and no skull fracture), moderate (>30
min amnesia and/or skull fracture) or severe (amnesia
>24 h, cerebral contusion or intracranial haematoma).
Early seizures (within 24 h) carry a worse progno-
sis overall, but do not increase the risk of subsequent
epilepsy. Up to 50% of patients with penetrating head
injury subsequently develop epilepsy.16 During the first
week after mild head injury, 2% develop seizures.17 The
risk of subsequent unprovoked seizures after traumatic
brain injury is significantly higher following severe head
injury than following moderate or mild head injury.18
Prophylactic AEDs reduce immediate and early seizures,
but do not influence subsequent epilepsy, death or neu-
rological disability.19
Inflammatory conditions
Multiple sclerosis and acute disseminated encephalomyelitis
Demyelinating disorders lead to a slightly increased risk
of seizures. Seizures were thought more likely with large
lesions, especially those involving the subcortical–cortical
junction; subsequent studies have not confirmed this.20
Acute symptomatic seizures at presentation are rare in
multiple sclerosis, although epilepsy may develop later.21
Conversely, seizures are a common presenting feature
of acute disseminated encephalomyelitis, ranging from
10%–20% in smaller series from the developed world to
30%–50% in larger studies in non-Western populations.22
copyright.
Sarcoidosis
Neurosarcoidosis occurs in 5% of patients with sar-
coidosis. Acute symptomatic seizures may occur in
the context of a meningitis or hydrocephalus. With
systemic immunosuppression, the granulomas may
regress; however, the residual gliosis and scarring can
lead to a long term epilepsy.23
Connective tissue diseases and systemic vasculitides
Estimates of neurological involvement in systemic lupus
erythematosus vary depending on the criteria used
and population studied. In a UK population, using the
American College of Rheumatology criteria, systemic
lupus erythematosus involved the nervous system in 57%.24
Seizures occur in 10%–20% but rarely at presentation.
The pathogenesis involves vaso-occlusive events and/or
systemic antibodies to cerebral tissue. Sjögren’s syndrome
affects the CNS in 20% of cases, sometimes with seizures.
Polyarteritis nodosa may present with an encephalopathy
including seizures. Seizures occur in <5% of Wegener’s
granulomatosis and Behçet’s disease and are uncommon
in rheumatoid arthritis and systemic sclerosis.
Cerebral vasculitis
Vasculitis can occur as a primary CNS phenomenon or
as part of a systemic inflammatory disease. Neurological
symptoms may be acute, subacute or chronic, and there
may or may not be systemic symptoms. Headaches, sei-
zures, stroke-like episodes and encephalopathy are well-
recognised presentations, sometimes with progressive

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Figure 6 Uncontrasted CT head showing a right subdural haematoma (left arrow), and subarachnoid blood (right arrow). Other
images revealed a skull fracture. Each of these can cause acute seizures.
cognitive decline, movement disorders, optic and other
cranial neuropathies.25
Immune-mediated encephalopathies
Anti-N-methyl-D-aspartate (NMDA) receptor antibody
encephalitis causes rapidly progressive encephalopathy,
neuropsychiatric features, dyskinesias and autonomic
disturbance. Seizures occur in about 75%.26 It is more
common in women and is associated with underlying
malignancy, usually ovarian teratoma, and is treatable
with intravenous immunoglobulin. Limbic encephalitis
occurs in association with anti-voltage-gated potassium
channel antibodies and presents with a more indo-
lent cognitive decline, neuropsychiatric features and
partial-onset seizures that may secondarily generalise
(figure 7). Treatment is with immunosuppression.27
Both NMDA receptor and limbic encephalitis can be
associated with underlying malignancy. Hashimoto’s
encephalopathy (steroid-responsive encephalopathy
with antithyroid antibodies (SREAT)) is characterised
by subacute encephalopathy, with seizures, tremor,
myoclonus and stroke-like episodes.
Metabolic causes
Electrolyte abnormalities may destabilise membrane
action potentials or cause local oedema, leading to sei-
zures. The CNS effects are determined by the speed of
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onset of the abnormality. The contributions of sodium,
magnesium and calcium to seizures are more signifi-
cant than potassium disturbances (though these cause
serious cardiac effects).
Hypoglycaemia
Hypoglycaemia most commonly develops with treat-
ment of diabetes mellitus, but other conditions may
lower glucose levels, for example, alcohol intoxication,
liver failure, insulinoma, disseminated malignancy,
Addison’s disease and hypothyroidism. Untreated
hypoglycaemia leads to loss of consciousness, seizures
and status epilepticus, but also focal neurological defi-
cits. Treatment is with 10% dextrose intravenously
(50% dextrose causes severe reactions after extravasa-
tion). Recurrent hypoglycaemia in a patient not tak-
ing insulin or sulphonylureas should prompt further
investigations, perhaps including short Synacthen test,
thyroid function, observed fast and imaging.
Hyperglycaemia
Partial-onset seizures and epilepsia partialis continua
are a recognised presentation of hyperosmolar non-
ketotic hyperglycaemia, particularly in older people,
where they may be the first manifestation of diabetes
mellitus. Seizures associated with hyperglycaemia are
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Figure 7 Axial FLAIR (left) and coronal T2 weighted (right) MRI images demonstrating high signal in the right medial temporal lobe
in limbic encephalitis and anti-voltage-gated potassium channel antibodies.
resistant to AEDs and respond best to correction of the
hyperglycaemia with insulin and rehydration.
Hyponatraemia
Delirium is the most common feature of hyponatrae-
mia. Seizures occur in 5%–15%, usually in those with
more severe hyponatraemia, and are reversed by cor-
recting the underlying cause in most cases.
Hypernatraemia
Clinical features commonly involve disturbances in
consciousness. Seizures are uncommon but may result
from either venous sinus thrombosis from dehydra-
tion or cerebral oedema from rapid correction of the
abnormality. Hypernatraemia must be corrected slowly
to prevent cerebral oedema from a large intracellular
influx of water.
Hypomagnesaemia
Magnesium is predominantly intracellular, and so
low serum magnesium may lag behind the intracellu-
lar depletion. Magnesium is important for potassium,
phosphate and calcium homeostasis. Magnesium defi-
ciency may result from dietary deficiency, malabsorp-
tion or excess renal loss. Common clinical features are
tetany, fasciculations, cardiac arrhythmia, confusion
and seizures. Correction of low magnesium levels dur-
ing seizures is with 4 g of magnesium sulphate over
20 min, and further 4 g infusions every 6 h as needed.
This may not be sufficient to terminate the seizures
and additional intravenous AEDs may be required.28
Hypermagnesiaemia does not generally cause seizures.
Hypocalcaemia
Calcium stabilises cell membranes and hypocalcaemia trig-
gers synchronised neuronal firing in the hippocampus.
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The major features are tetany and carpopedal spasm,
and later confusion, loss of consciousness and seizures.
Important causes include renal failure, acute pancreatitis
and endocrine aetiologies – hypo – and pseudohypo-par-
athyroidism and vitamin D deficiency. Treatment is with
calcium replacement.
copyright.
Hypercalcaemia
Hypercalcaemia most commonly causes stupor and coma;
seizures are unusual. Causes include acute renal failure,
hyperparathyroidism, malignancy (paraneoplastic phe-
nomena and bone invasion), bone metabolism disorders,
immobility and drug toxicity. The pathogenesis of seizures
is unclear. Seizures are rapidly corrected by correcting the
hypercalcaemia with intravenous normal saline, loop diu-
retics and bisphosphonates.
Liver failure
Hepatic encephalopathy presents with subtle cognitive
and behavioural changes, progressing to disorientation,
worsening somnolence, tremor and asterixis. Seizures
are rare and mainly occur in advanced disease.
Toxic causes
Some toxins and medications cause seizures directly,
and others through acute withdrawal. Alcohol-related
seizures are probably the commonest cause of acute
symptomatic seizures in the UK (box 2).
Recreational drugs
Amphetamines, 3,4-methylenedioxy methampheta-
mine (MDMA) and cocaine each cause seizures in over-
dose. Seizures are more common in heroin users than
in the general population and most likely within 24 h
of acute intoxication. Benzodiazepines and barbiturates
may cause seizures during withdrawal owing to GABA
receptor downregulation. Cannabis probably does not

provoke seizures and likewise other hallucinogenic
agents, except at high doses.30
Other toxins
Animal toxins may cause seizures, including tetrodo-
toxin (from pufferfish), saxitoxin (from microorganisms
consumed by clams and other shellfish) and ciguatera
poisoning (reef fish). Fungal toxins such as from aman-
ita mushroom species (usually inadvertently consumed
by young children) can produce seizures. Several plant
toxins, for example, water hemlock, jimsonweed,
Atropa belladonna, squill plant, azalea, bleeding hearts
and Christmas rose can also produce seizures. Other
toxic causes are carbon monoxide, heavy metals (lead
and tin) and organic solvents, in severe intoxication.31
Pregnancy and eclampsia
Pre-eclampsia and eclampsia comprise a pathological
continuum caused by impaired placental formation.
Eclampsia is defined as seizures and/or coma in the
context of hypertension (systolic >140 mmHg, diasto-
lic >90 mmHg), and proteinuria (0.3 g/24 h) with
onset after the 20th week of pregnancy. It may present
with neurological symptoms and can occur several days
postpartum.32 Neurological symptoms include reduced
attention, memory and orientation, psychosis, visual dis-
turbance, seizures, headache, cortical and retinal blind-
ness, as well as focal neurological deficits. Definitive
treatment is delivery of the infant; interim manage-
ment relies on antihypertensives, for example, methyl-
dopa, labetalol, diuretics and nifedipine.33 Magnesium
is effective in preventing pre-eclampsia progressing to
eclampsia and in treating eclamptic seizures. Diazepam
and phenytoin are less effective in seizure control.34
Not all seizures in the perinatal period are due to
eclampsia; other conditions, such as posterior reversible
encephalopathy syndrome and venous sinus thrombosis,
may mimic eclampsia, and thrombotic thrombocyto-
penic purpura (microangipathic haemolytic anaemia, low
platelets, renal failure, fever and neurological features,
including seizures) is also more common in pregnancy.
Treatment
The management priority is treatment of the underlying
aetiology. Temporary use of AEDs may help suppress
seizures while the underlying aetiology is still active;
however, there is little evidence that this reduces the
risks of subsequent epilepsy. Prophylactic AEDs reduce
the risk of post-traumatic seizures in the first week
following head trauma, but do not change the risk of
epilepsy, or overall outcome following traumatic brain
injury.35 Using prophylactic AEDs in this context there-
fore remains controversial. However, many experts
recommend treatment for 1 week following severe
head injury or subarachnoid haemorrhage to prevent a
seizure-related exacerbation of raised intracranial pres-
sure. In the acute setting, a single self-limiting seizure
as part of a reversible problem usually does not war-
rant therapy. Recurrent seizures or status epilepticus
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Box 2 Alcohol-related seizures
Alcohol-related seizures, through intoxication or withdrawal,
account for up to 40% of emergency seizure presentations.29
Acute intoxication causes direct neuronal toxic effects, reduc-
ing inhibitory activity. Alcohol is a sedative; its acute withdrawal
can provoke seizures through a hyperexcitable state from down-
regulation of γ-aminobutyric acid (GABA)-ergic activity during
chronic alcohol use. Several metabolic abnormalities associated
with alcoholism can trigger acute seizures; hypomagnesaemia
(through poor nutrition) and hypoglycaemia (through depleted
liver glycogen) can both accompany chronic alcohol abuse, and
hyponatraemia can develop in liver disease. Patients abusing
alcohol more likely suffer vascular events (traumatic haemato-
mas, stroke, hypertensive haemorrhage) and head trauma lead-
ing to acute symptomatic seizures, as well as increasing the risk
of subsequent epilepsy. They also more likely abuse other sub-
stances and seizures may result from intoxication with another
agent.
Alcohol withdrawal seizures respond best to benzodiaz-
epines. Clinicians should seek and treat electrolyte abnormali-
ties, acute intracranial pathology, infection and drug overdose.
There is little evidence regarding starting antiepileptic drugs
in patients with recurrent alcohol-related seizures not clearly
caused by alcohol withdrawal or other secondary cause; this
decision must be individualised and it is important to consider
the possibility of head injury, metabolic derangements and
infection. For patients who understand the importance of good
compliance, treatment should be offered. Using antiepileptic
copyright.
drugs that are not liver metabolised seems logical, although
there is no evidence to support this.
(which may be non-convulsive) require intervention.
Most authorities also recommend giving thiamine and
intravenous glucose to patients presenting with recur-
rent seizures or status epilepticus.
Decisions about choosing and continuing AED treatment
following an acute symptomatic seizure are not straight-
forward, with no clear guidelines available. In general,
long term AED treatment is reserved for those with resid-
ual structural abnormalities on MRI. Rates of epilepsy are
highest following severe head injury,18 36 and following
viral encephalitis with acute symptomatic seizures,10 jus-
tifying a more cautious approach to AED withdrawal in
these contexts. There is a strong argument for long term
AED treatment following an acute symptomatic seizure in
HIV patients, although enzyme-inducing drugs are best
avoided. We have attempted to summarise some of these
points, and offer suggestions for the treatment of acute
symptomatic seizures, in the online supplementary appen-
dix 1. This summary of our current practice is based on
the evidence available and our own experience, with the
caveat that these are certainly not black and white deci-
sions, and that the specific details of each case (including
the number and timing of seizures, and location of pathol-
ogy) will vary. In all cases, the decision to start treatment,
and how long to continue treatment, must be individual-
ised, taking into account potential medication side-effects,
employment status and, often of most relevance, driving
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Box 3 Investigation of acute symptomatic seizures

Blood tests
Essential tests FBC, U+E, liver function tests, C reactive protein, glucose, magnesium, calcium, phosphate
Clinical feature Tests to consider
Evidence of sepsis Blood cultures and urinalysis
Systemic features (rash, arthralgia etc), Neuroinflammatory screen:
suggestive changes on MRI and CSF ESR, antinuclear antibody, antineutrophil cytoplasmic antibody, antidouble-stranded
DNA, antiextractible nuclear antigen, ACE level, serum complement, antiphospholipid
antibody, anticardiolipin antibody and lupus anticoagulant
Risk factors in history HIV, tuberculosis PCR/T-Spot
Clinical suspicion Toxicology screening for drugs of abuse and alcohol
Serum ammonia
Underlying malignancy Paraneoplastic antibody screen, N-methyl-D-aspartate (NMDA) receptor and
voltage-gated potassium channel antibodies
Cognitive or neuropsychiatric features, NMDA, potassium channel antibodies, thyroid antibodies
movement disorders
Neuroimaging
Almost all patients will require brain imaging. The main choice lies between MRI and CT, though other modalities may be needed.
CT scan of head ■ Quick, cheap and readily available

■ Avoids need for sedation

■ Demonstrates blood, abscess, tumours, oedema, infarcts, bony injuries and changes

accompanying venous sinus thrombosis

MR scan of brain ■ Differentiates between acute and chronic ischaemia

■ Better imaging of posterior fossa and brainstem

■ Better demonstration of changes in encephalitis and inflammatory conditions

copyright.
■ More likely to show smaller mass lesions and vascular malformations

CT or MR cerebral venogram Consider with papilloedema and features of raised intracranial pressure, focal
neurological signs
Lumbar puncture
We advise a low threshold for performing a lumbar puncture in patients with acute symptomatic seizures (providing no
contraindications), particularly if there is no head trauma or metabolic derangement, and no clear aetiology demonstrated on
examination or neuroimaging.
Opening pressure Raised in;
■ Venous sinus thrombosis

■ Brain swelling – meningitis (especially cryptococcal), encephalitis, trauma

Cell count ■ >5 White cells mm-3 is abnormal

■ Neutrophils – consider bacterial meningitis

■ Lymphocytes – consider viral meningitis or encephalitis, mycobacterial, and fungal

infection
■ Mixed or either cell type predominant in inflammatory conditions

■ Prior antimicrobial treatment may give a false negative result

Protein Raised protein suggests active central nervous system (CNS) pathology, infection,
inflammation, malignancy or haemorrhage
Glucose Significantly reduced in bacterial infection (ratio with serum glucose <60% is abnormal)
Other infectious tests Viral PCR
Cryptococcal antigen
India ink stain
Ziehl–Neelsen stain, tuberculosis PCR and culture
JC virus PCR
Cytology (+/- immunophenotyping) Malignant cells
Xanthochromia If subarachnoid haemorrhage suspected

Continued

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Box 3 Continued

EEG
Although non-specific (especially in the older people), the EEG can sometimes help:
■ distinguishing seizures from non-epileptic attacks

■ identifying non-convulsive status epilepticus

■ in showing diffuse slowing of background rhythms, a non-specific abnormality which may be seen postictally, following

traumatic brain injury or CNS infection and accompanying any encephalopathy

■ in showing focal slowing or periodic lateralising epileptiform discharges, which occur with any localised pathology,

including viral encephalitis, tumours and vascular events

CSF, cerebrospinal fluid; FBC, full blood count; ESR, erythrocyte sedimentation rate.

Table 1 Drugs used for acute symptomatic seizure

Drug Key points

Benzodiazepines Lorazepam 4 mg bolus, repeated after 10 min if necessary.

Phenytoin
Barbiturates (phenobarbital
and thiopentone)
Rectal diazepam and buccal midazolam are alternatives.
Short course of oral clobazam useful in patients with recurrent seizures that do not develop into status epilepticus.
Main side-effects are sedation and respiratory depression – airway management and ventilatory support in a critical care
facility may be required.
Intravenous loading (15 mg/kg over 20 min) effective in terminating tonic-clonic and partial status epilepticus.
Cardiac monitoring required (risks of arrhythmias).
Long term side-effects, complex drug interactions and pharmacokinetics make this a less attractive maintenance agent.
Fosphenytoin is considerably more expensive, but has the advantages of fewer injection sites and cardiovascular side effects,
and can be given intramuscularly.
Third line agents if benzodiazepines and phenytoin are unsuccessful.

copyright.
Respiratory depression and hypotension necessitate admission to a critical care facility.
Long half-life often results in prolonged ventilation.
Propofol Primarily used as an anaesthetic agent, but more rapid seizure control, less cardiovascular side effects and shorter half-life
than barbiturates.
Overly rapid weaning can cause rebound seizure activity.
Sodium valproate Increasingly favoured over phenytoin in the acute situation, with few side-effects when given rapidly at high doses
(25 mg/kg over 10 min).37
Effective for other seizure types (absence, myoclonic).
Should be avoided in patients with liver impairment.
Risk of congenital malformations limits use in women of child-bearing age.
Levetiracetam Open label studies have demonstrated efficacy of intravenous loading in status epilepticus38 and in critically ill patients with
acute symptomatic seizures.39
Usually well tolerated and therapeutic oral dose (1000 mg daily) achievable over several days or quicker.
Can be started orally alongside more aggressive treatment, allowing the withdrawal of phenytoin, barbiturates or propofol
more safely.
Useful when trying to avoid drug interactions (eg, patients on warfarin, HIV patients).

status. AED selection in the acute situation is governed
by efficacy, speed of onset of seizure control, side effect
profile and comorbidities (table 1).
Prognosis
The overall risk of seizure recurrence following an
acute symptomatic seizure is significantly lower than
that following a single unprovoked seizure.40 In a study
of acute symptomatic seizures (within 1 week) follow-
ing stroke, traumatic brain injury or CNS infection,
the 10-year risk of a subsequent unprovoked seizure
was 18.7%. This compared with a 64.8% rate of sei-
zure recurrence (after at least 1 week) following an
unprovoked seizure.41 Despite this, the 30-day mor-
tality rate was higher following acute symptomatic
seizures compared with ‘unprovoked’ seizures, reflect-
ing the associated CNS pathology. These differences
support the notion that acute symptomatic seizures
are separate from epilepsy, and that, in general, these
patients do not have an underlying predisposition to
epilepsy.
The underlying aetiology broadly dictates prognosis
following acute symptomatic seizures. For example,
acute seizures from metabolic derangement do not usu-
ally carry an increased risk of subsequent epilepsy. For
most other aetiologies, for example, trauma, infection,

Practical Neurology 2012;12:154–165. doi:10.1136/practneurol-2012-000244 163

 REVIEW
and vascular causes, patients with acute symptomatic
seizures are at higher risk for subsequent epilepsy than
patients without.10 18 35 Perhaps research into the cellu-
lar and molecular mechanisms underlying epileptogen-
esis will identify interventions, possibly before seizure
onset, to prevent subsequent epilepsy.42
Acknowledgements The authors thank Dr Peter Bergin,
New Zealand, for reviewing this paper and Dr Inder
Sawhney, Swansea, for his helpful comments.
Competing interests DM has no competing interests. RP
has received travel grants from UCB Pharma and Eisai.
Provenance and peer review Not commissioned;
externally peer reviewed.
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■ Acute symptomatic seizures differ from epilepsy in terms of the
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Practical Neurology June 2012 Vol 12 No 3 165
Corrections

doi: 10.1136/practneurol-2012-000244corr1
Powell R, McLauchlan DJ. Acute symptomatic seizures (Pract Neurol 2012;12:154–65).
McLauchlan DJ is the first author of this paper not Powell R. We would like to apologise for any
embarrassment caused to the lead author by this oversight.

Practical Neurology 2012;12:263–265. doi:10.1136/practneurol-2012-000280 265