Blackwell Science, LtdOxford, UKCHACephalalgia0333-1024Blackwell Science, 200323994997Clinical CorrespondenceThunderclap headache associated with reversible vasospasm and PLESDW Dodick et al.

CLINICAL CORRESPONDENCE

Thunderclap headache associated with reversible vasospasm and
posterior leukoencephalopathy syndrome
DW Dodick, EJ Eross, JF Drazkowski & TJ Ingall
Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA

David W. Dodick, Department of Neurology, Mayo Clinic, 13400 East Shea Blvd,
Scottsdale, AZ 85259, USA. Tel. + 480 301 8112, fax + 480 301 8451, e-mail
dodick.david@mayo.edu Recived 26 March 2002, accepted 10 December 2002

Case report
A 46-year-old woman with a past medical history of
episodic migraine and benign sexual headache was
in good health until she experienced an explosive,
sudden and severe occipital headache while having
a bowel movement. There was no associated loss of
consciousness or awareness. The headache, however, was associated with nausea and neck pain/
stiffness. The headache intensity diminished over
several hours. Two days later, she experienced a
recurrent more prolonged thunderclap headache,
whereupon she was taken immediately to hospital.
In the emergency department (ED), she was hypertensive (190–200/110–120) and mildly drowsy.
Examination revealed no meningeal, long tract,
focal, or lateralizing neurological signs. Furthermore, there was no evidence of hypertensive retinopathy or papilloedema.
During her evaluation in the ED, she had a witnessed generalized tonic clonic seizure. A computed
tomography (CT) scan of the brain and lumbar puncture were normal. Blood work revealed a mild
thrombocytosis (437K), but CBC, electrolytes, ESR
(9), ANA (0.4), hypercoagulable profile, TSH, urinalysis, and serum chemistry were normal. A magnetic
resonance imaging (MRI) scan of the brain revealed
T2 signal abnormalities in the posterior parietooccipital lobes with a small area of increased diffusion-weighted signal in the left occipital lobe (Figs. 1
and 2). There was no evidence of gadolinium
enhancement. On the fourth hospital day, a fourvessel cerebral angiogram revealed diffuse multifocal vasospasm involving the posterior and anterior
circulation (Fig. 3). There was no evidence of an
intracranial aneurysm or arteriovenous malformation. A diagnosis of ischaemic stroke secondary to
CNS vasculitis was made and the patient was treated
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with high-dose intravenous methylprednisolone
and warfarin. The patient was transferred to our
institution for in-patient video-EEG monitoring
because of the generalized tonic-clonic seizure. During her hospitalization at our institution, follow-up
MRI scans (on days 6 and 13 after presentation)
revealed resolution of the T2 signal abnormalities
(Fig. 4). Fifteen days after presentation, a follow-up
magnetic resonance angiogram was normal.
The patient was treated with lisinopril 5 mg, her
blood pressure ranged from 130 to 140 systolic and
80 to 90 diastolic. No further seizures occurred and
video-EEG monitoring over 48 h was normal. An
evaluation for secondary causes of hypertension was
unremarkable. Warfarin was discontinued and the
patient was discharged in normal neurological condition and headache free. She remained asymptomatic on lisinopril 4 months later.

Discussion
This patient presented with recurrent thunderclap
headache and a generalized tonic-clonic seizure
within a 48-h period in the setting of severe
paroxysmal hypertension. MRI revealed T2 and diffusion-weighted signal hyperintensity involving the
posterior parieto-occipital lobes, and an angiogram
showed diffuse, multifocal, segmental vasospasm
involving the circle of Willis and its branches. The
clinical presentation and imaging changes were consistent with posterior leukoencephalopathy syndrome (PLES). However, the presence of diffuse
cerebral vasospasm led to the erroneous diagnosis of
ischaemic stroke secondary to CNS vasculitis and
inappropriate treatment with high-dose intravenous
methylprednisolone and warfarin.
Headache occurs in approximately 20% of patients
during a hypertensive emergency, and although the
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Thunderclap headache associated with reversible vasospasm and PLES

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Figure 1 (a,b) The initial FLAIR MRI sequences reveals signal abnormalities located in the posterior parieto-occipital lobes.

headache is usually throbbing and non-distinct (1),
thunderclap headache has been reported in a recent
report of a patient with hypertensive encephalopathy with PLES (2). The clinical presentation and MRI
changes in the patient described here are very
similar to those described in this recent report and
are suggestive of PLES secondary to severe
hypertension.
PLES is a rapidly evolving neurological condition
characterized by headache, nausea and vomiting,
visual disturbances, altered mental status, decreased
alertness, seizures, and, occasionally, focal neurological signs (3, 4). PLES is associated with an abrupt
and severe increase in blood pressure in most cases,
including patients with eclampsia or renal disease
with hypertension. Although hypertensive encephalopathy is the most common cause of PLES, there
have been a number of cases described which
occurred in the absence of severe hypertension. The
syndrome is also seen in patients treated with
immunosuppressive drugs such as intravenous
immunoglobulin, cyclosporin A, tacrolimus, and
© Blackwell Publishing Ltd Cephalalgia, 2003, 23, 994–997

interferon-alpha (3). The main finding in neuroimaging and autopsy studies is posterior white matter
oedema, particularly involving the parietal and
occipital lobes, which may spread to the basal ganglia, brainstem, and cerebellum (5, 6). Complete clinical and radiological recovery often occurs with
prompt anti-hypertensive treatment or withdrawal
of the immunosuppressive drug. Occasionally, the
clinical features and CT or standard MRI findings
may be indistinguishable from a bilateral posterior
cerebral artery stroke syndrome. Thus, early recognition of PLES is essential.
To the best of our knowledge, diffuse cerebral
vasospasm, as seen in this case, has not been previously reported in patients with PLES. The mechanism of the reversible vasospasm in this patient is
unclear. Reversible vasospasm of the cerebral vasculature is recognized to occur in patients with
idiopathic thunderclap headache, following subarachnoid haemorrhage (SAH) due to a ruptured
saccular aneurysm, and in association with pheochromocytoma,
eclampsia
sympathomimetic

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DW Dodick et al.

Figure 3 The cerebral angiogram (hospital day 4) reveals
diffuse, multifocal, segmental vasospasm in the posterior
circulation. Similar findings were present in the anterior
circulation.

Figure 2 The initial diffusion-weighted image show an
abnormality existing in the left occipital lobe.

(amphetamine and cocaine) and ergotamine drug
intoxication, angiographic contrast material, surgical
manipulation, and closed head injury (7–15). It has
also been described in patients with ‘vascular’ headache, migraine, and ‘isolated benign cerebral vasculitis’ (16–18). The mechanism of vasospasm in this
patient and in patients with PLES is unclear, but may
be related to a loss of autoregulation, resulting in
dilatation of cerebral arterioles and disruption of
the blood–brain barrier (BBB). In animals, arteriolar
resistance increases proportionately as blood pressure rises until a threshold is reached at which autoregulation fails segmentally, and the mechanical
effect of elevated pressure causes passive segmental
vasodilation (19–21).
The recognition that reversible segmental vasospasm can occur in patients with PLES has important
clinical implications. As seen in this case, an acute
neurological illness which is associated with cerebral
vasospasm and acute parenchymal changes on MRI
can easily be mistakenly diagnosed as CNS vasculitis and result in the inappropriate use of immuno-

Figure 4 Follow-up FLAIR MRI (14 days after initial MRI) is
essentially normal.

© Blackwell Publishing Ltd Cephalalgia, 2003, 23, 994–997

Thunderclap headache associated with reversible vasospasm and PLES
suppressive and anticoagulant therapy. Indeed,
recognizing the clinical and MRI features of this disorder would obviate the need for a cerebral angiogram. Failure to recognize this syndrome could also
lead to failure to lower blood pressure acutely and
aggressively, the definitive treatment of PLES, especially when the diagnosis of ischaemic stroke is erroneously made. It should also be recognized that
isolated CNS vasculitis is not known to present with
thunderclap headache in the absence of SAH, and
these patients often have abnormal spinal fluid
examinations (22). Furthermore, isolated CNS vasculitis is invariably restricted to blood vessels which
are <0.5 mm in diameter and not, as in this case,
large blood vessels that constitute the circle of Willis
and its second-order branches.

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