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Self-assessment questions

Headache, blindness and a
seizure after childbirth
H Mehta,1 T Khan,1 T F Ismail,1 A Rogers,1 A Wallis,1
D Collas,1 W R J Wallis,1 M J van der Watt,1
D J Werring1,2
A previously fit and well 17-year-old
primiparous woman presented 5 days
following the uncomplicated delivery of
her first child with a gradual onset, severe,
throbbing, predominantly left sided headache. There was no nausea, vomiting,
neck stiffness or photophobia. Her past
medical history was unremarkable, apart
from heterozygosity for factor V Leiden,
for which she was screened because of a
history of thrombophilia in her mother.
On initial assessment, no abnormality
was detected other than an elevated blood
pressure of 180/100 mm Hg. There was
no evidence of oedema or proteinuria.
Two days later, her visual acuity deteriorated over 12 h from 6/6 to perception of
hand movements bilaterally, precipitating
referral to the medical team. She then had
a generalised tonic–clonic seizure, which
was terminated within 5 min using intravenous magnesium and diazepam. She
was subsequently loaded with phenytoin
with no further seizures. On examination
by the medical team, blood pressure
remained elevated at 180/110 mm Hg.
Visual acuity was reduced to perception
of hand movements, pupillary responses
were normal and there was no papilloedema. Tone, power, coordination and
sensation were normal throughout.
Reflexes were brisk, particularly in the
left arm, and the plantars were extensor
bilaterally. Other than mildly elevated
inflammatory markers compatible with
recent parturition, her blood tests and
urine dipstick were unremarkable.

QUESTION 1: WHAT IS THE DIFFERENTIAL
DIAGNOSIS?
At this stage, the differentials that need
to be considered in a peripartum woman
with headache, neurological deficits,
1

Department of Medicine, Watford General Hospital,
Watford, UK; 2 Institute of Neurology, University College
London, National Hospital for Neurology and
Neurosurgery, London, UK
Correspondence to: Dr D J Werring, Stroke Research
Group, Department of Brain Repair and Rehabilitation,
Institute of Neurology, Queen Square, London WC1N
3BG, UK; d.werring@ion.ucl.ac.uk

Postgrad Med J 2008 Vol 84 No 996

seizures and a family history of thrombophilia include:
c
c
c
c
c

pre-eclampsia/eclampsia
dural venous sinus thrombosis
cerebral infarction
cerebral haemorrhage
posterior reversible encephalopathy
syndrome (PRES).

QUESTION 2: HOW SHOULD THE PATIENT
BE FURTHER INVESTIGATED TO RESOLVE
THE DIFFERENTIAL DIAGNOSIS?
The patient’s primiparity, young age, and
family history of thrombophilia are significant risk factors for pre-eclampsia.1
Eclampsia—characterised by hypertension, proteinuria and neurological symptoms including visual disturbance and
seizures—usually occurs in the last trimester or within a few days of delivery, but
may occur up to 23 days post-partum.2
Eclampsia is usually associated with significant proteinuria (.300 mg/24 h), but
urine dipsticks are not reliable in excluding this; furthermore, even without proteinuria, the index of suspicion should
remain high in a peripartum patient with
hypertension, visual disturbance and seizures.1 2 Cerebrovascular
disorders—
including cerebral infarction and cerebral
venous sinus thrombosis—are rare complications of pregnancy and the puerperium,3 but must be carefully considered in
the context of both the inherited and
acquired thrombophilic tendency of the
patient, and the presence of focal neurological deficits complicated by seizures.
Cerebral haemorrhage can also give rise to
these features, and cannot be reliably
excluded without brain imaging. The
radically different management strategies
needed (anticoagulation for cerebral
venous sinus thrombosis, possible intraarterial thrombolysis for basilar artery
thrombosis or antiplatelet agents for
other types of cerebral infarction, and
aggressive medical and supportive therapy to reduce haematoma expansion for

haemorrhage) make the need for urgent
neuroimaging all the more pressing.
A computed tomography (CT) scan of
the head was undertaken and revealed
subtle reduced attenuation in bilateral
occipitoparietal regions, worse on the
right than the left, but no evidence of
venous sinus thrombosis (fig 1). CT may
show acute thrombus in the sagittal or
lateral sinuses, but even with contrast
techniques is not sufficiently sensitive to
completely exclude cerebral venous sinus
thrombosis.4 5 In view of the hypercoagulable state engendered by recent pregnancy, and the patient’s factor V Leiden
status, urgent magnetic resonance imaging (MRI) with MR venography and
diffusion weighted sequences was
arranged to exclude more definitively
venous sinus thrombosis or infarction.
The venous sinuses were patent but the
FLAIR (fluid attenuated inversion recovery) sequences revealed patchy increased
signal in a similar distribution to the
abnormalities noted on CT (fig 2). The
diffusion weighted images showed no
significant restriction of diffusion, suggesting vasogenic oedema rather than the
cytotoxic oedema typical of cerebral
infarction, which causes restricted diffusion. These characteristic neuroradiological findings in conjunction with the
patient’s clinical presentation and the
absence of evidence of venous sinus
thrombosis suggested a diagnosis of posterior reversible encephalopathy syndrome (PRES).

Figure 1 Axial CT scan of the head showing
subtle, patchy low attenuation in bilateral
parieto-occipital regions.
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Self-assessment questions

Figure 2 MRI of the brain (axial FLAIR
sequence) at initial presentation showing patchy
parieto-occipital increased signal (arrows).

QUESTION 3: HOW SHOULD THE PATIENT
BE MANAGED?
The management priorities are to remove
any precipitants, aggressively lower blood
pressure and treat any seizures.
Accordingly, intravenous labetalol was
started to reduce the patient’s blood
pressure to ,140/80 mm Hg, a manoeuvre which could have been deleterious
had primary cerebral infarction and
venous sinus thrombosis not been confidently excluded. Anticonvulsants are
used as in any setting of acute prolonged
generalised seizures.6 In our patient, phenytoin was continued at the usual oral
maintenance doses for seizure prophylaxis
and her electrolytes were carefully monitored and tightly controlled.
Over the next 48 h, the patient
reported that her vision had returned to
normal apart from a small area of blurriness in her left hemi-field, which resolved
fully over the next few days. The headache also subsided and at follow-up
8 weeks later, she was asymptomatic
with no further seizures or visual disturbance. Her blood pressure was well
controlled on oral labetalol and a repeat
MRI brain showed complete resolution of
the original changes (fig 3).

DISCUSSION
PRES is an unusual but readily treatable
cause of acute headache, altered consciousness, visual disturbance and seizures.7 Since the original description of
the syndrome in 1996, a number of
triggers have been characterised for the
556

Figure 3 MRI of the brain (FLAIR sequence) at
8 weeks follow-up.
syndrome including pregnancy (sometimes with eclampsia), severe hypertension, immunosuppressive treatment and
uraemia.7–9 The exact pathogenesis
remains obscure,7 though it is thought
that disturbed cerebral autoregulation
with endothelial injury or dysfunction
results in increased vascular permeability
in the posterior circulation.7 10 11 The
resultant leakage of fluid across the
blood–brain barrier impairs neuronal
function causing an encephalopathy
(headache, impaired consciousness, seizures) with pronounced visual disturbance.10 Untreated, this vasogenic
oedema may compromise the integrity
and function of the local cerebral microcirculation, thereby producing cell death
and permanent neurological sequelae.12 13
Structures supplied by the anterior circulation may be involved, though the
disorder shows a predilection for posterior
vascular territories.7 10 This may reflect
the relative paucity of sympathetic fibres
innervating the posterior circulation in
comparison to the anterior circulation,10 14
making the posterior vasculature more
vulnerable to failure of autoregulation and
endothelial leakage.11 14
MRI with FLAIR and diffusion
weighted sequences is the modality of
choice for clarifying the diagnosis and
distinguishing the syndrome from cerebral
infarction or venous sinus thrombosis.12 13
Rapid early diagnosis is essential as blood
pressure lowering may worsen outcome
from cerebral infarction due to thrombotic occlusion of the vertebrobasilar artery
or cerebral venous sinuses, yet this measure is the cornerstone of managing PRES.

T2 weighted sequences (especially FLAIR)
reveal patchy hyperintense lesions, predominantly affecting but not necessarily
confined to the posterior white matter
(fig 1).12 Diffusion weighted imaging
techniques can be used to seek the
restricted diffusion characteristic of cytotoxic oedema in cerebral infarction, by
contrast with the generally increased
diffusion due to vasogenic oedema seen
in PRES.15 However, PRES can also result
in permanent cerebral infarction,11 causing
a more complex pattern of diffusion
changes.
The management of PRES is directed
towards, wherever possible, removal of
the original insult that precipitated
endothelial dysregulation, and aggressive
control of blood pressure and seizures.10
Worsening hypertension escalates further
endothelial damage, thereby creating a
vicious circle of further cerebral injury and
worsening hypertension.9 Generalised seizures may result, increasing cerebral oxygen consumption and exacerbating
cerebral oedema at a time when cerebral
autoregulation and microvascular integrity are already compromised. Thus, if
untreated, PRES may not be reversible but
can result in severe neurological sequelae
or even death. Blood pressure should
therefore be expeditiously lowered in a
controlled manner using parenteral antihypertensives such as labetalol with invasive blood pressure monitoring.9 10 Sodium
nitroprusside and glyceryl trinitrate may
also be used, but, by increasing cerebral
vasodilatation, may worsen vasogenic
oedema.9 While doubt remains regarding
the safety of the latter drugs in this
context, and in the absence of compelling
contraindications, labetalol may therefore
be the agent of choice in PRES.10 Seizures
should be promptly arrested with intravenous lorazepam followed by phenytoin

Learning points
Posterior reversible encephalopathy
syndrome (PRES) is a rare but
potentially reversible cause of
headache, visual disturbance and
seizures.
c Early recognition and prompt treatment
is required to prevent permanent
neurological sequelae or death.
c Early diagnosis is facilitated by prompt
neuroimaging with magnetic
resonance imaging.
c Treatment is directed towards
removing precipitants, lowering blood
pressure, and controlling seizures.
c

Postgrad Med J 2008 Vol 84 No 996

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Self-assessment questions
(or magnesium sulfate in the obstetric
setting if pre-eclampsia is suspected).6 10
The rarity of the condition and its diverse
aetiologies are likely to preclude randomised controlled trials. Thus, management is likely to continue to be guided
by our limited understanding of the
underlying pathophysiology of PRES,
highlighting the urgent need for more
basic and clinical research.

neurological sequelae and even death in
the absence of prompt treatment.

6.
7.

FINAL DIAGNOSIS
Posterior reversible encephalopathy syndrome (PRES).
Funding: None
Competing interests: None.

8.
9.
10.

Patient consent: Obtained

CONCLUSIONS

Accepted 24 July 2008

PRES is a rare but treatable cause of
headache, visual disturbance and seizures.
Clinicians from a variety of backgrounds
and disciplines should consider PRES in
the differential diagnosis of headache,
altered consciousness and seizures. The
index of suspicion should be high in
patients who are peripartum or who have
received immunosuppressive drugs with
potentially neurotoxic adverse effects.
The importance of early recognition is
underscored by the potential reversibility
of the condition and the development of

Postgrad Med J 2008;84:555–557.
doi:10.1136/pgmj.2007.063438

11.
12.

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Postgrad Med J 2008 Vol 84 No 996

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Headache, blindness and a seizure after
childbirth
H Mehta, T Khan, T F Ismail, A Rogers, A Wallis, D Collas, W R J Wallis,
M J van der Watt and D J Werring
Postgrad Med J 2008 84: 555-557

doi: 10.1136/pgmj.2007.063438
Updated information and services can be found at:
http://pmj.bmj.com/content/84/996/555

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