Stroke in lupus and APS
LCD de Amorim et al.
532
Sneddon’s syndrome frequently presents with leu-
coaraiosis and small lacunar infarcts.31
Sneddon’s syndrome is not a unique entity.
Comparison of patients with or without aPL
showed that the livedo reticularis was clearly
larger in aPL-negative patients who, nevertheless,
did not develop thrombocytopenia; and seizures
and clinically audible mitral regurgitation were
more frequently observed in aPL-positive
patients.32 It is possible that some of the patients
diagnosed with this syndrome will develop APS or
SLE over time.
Haemorrhagic stroke
Haemorrhagic stroke frequency is very low and rep-
resents approximately 10% of all strokes.33 It occurs
more frequently in patients over 50 years of age with
hypertension.33 Intraparenchymatous haemor-
rhagic stroke is three times more common in SLE
patients than in healthy individuals due to endothe-
lial dysfunction characteristic of the disease that
leads to a rupture of intracerebral vasculature.1,8
SAH occurs in approximately 5% of all strokes
and affects mainly young women, with a peak age
of approximately 50 years.1 The risk of SAH is four
times more common in SLE patients compared to
healthy individuals, and the disruption of vascular
aneurysm is the main cause.34 Older age, high ster-
oid intake, previous transfusions, cerebral vascu-
litis, kidney disease, and hypertension are risk
factors for its occurrence.34 As in the general popu-
lation, SAH in SLE occurs in people under age 50
years, in the first five years of disease onset, and has
a mortality rate ranging from 25% to 35%.1,35
Importantly, a study observed an earlier onset of
SAH in SLE patients than in the general popula-
tion (44.5 versus 57.7 years), and SLE patients had
a higher risk of SAH, with an incidence rate ratio of
4.84 (p < 0.001).35 In addition, age (HR 1.03; 95%
95% CI 1.01–1.05), platelet transfusion (HR 2.75;
95% CI 1.46–5.17), red blood cell transfusion (HR
7.11; 95% CI 2.81–17.97), and a mean daily steroid
dose >10 mg of prednisolone or the equivalent (HR
4.36; 95% CI 2.19–8.68) were independent risk fac-
tors for the new onset of SAH.36
Aneurysm rupture is the most common cause
(85%) of SAH followed by a perimesencephalic
SAH, not aneurysmal haemorrhage (10%), and
the other 5% is represented by other rare
causes.37 Three different mechanisms of SAH in
SLE have been described: multiple saccular aneur-
ysms, distal fusiform aneurysms with aberrant
morphology in uncommon locations, and angio-
graphic-negative SAH.38
Lupus
Central venous thrombosis (CVST)
CVST is an unusual cause of cerebrovascular dis-
ease, most of the time under-recognized. It usually
presents as a refractory headache, sometimes asso-
ciated with an epileptic seizure, focal deficits, or
intracranial hypertension syndrome. Its association
with SLE has been documented, mostly through
case reports, and the use of corticosteroids and
lumbar puncture may be risk factors that increase
the incidence of this condition.39 The association of
APS with CSVT is much better recognized as the
most common acquired thrombophilia associated
with this syndrome, and it requires a high sense
of awareness of this diagnosis, since early treatment
implicates a better prognosis.39
Other CNS manifestations
Vascular cognitive impairment has been increas-
ingly recognized as a major cause of neurological
deficits in the older population and is frequently
associated with white matter lesions burden.40
In SLE, this pattern of CNS lesions has been
increasingly studied recently, but its clinical signifi-
cance is not very clear yet.41 In APS, although the
same finding was expected, a study by
Arvanitakis42 studying post-mortem brains did
not show an increased incidence of infarcts in this
population. SLE itself can cause stroke rarely
due to vasculopathy or vasculitis, and true vascu-
litis is rare. 5
Patient workup
When evaluating a patient with a suspected cere-
brovascular disease caused by SLE, it is important
to evaluate some aspects of the medical history and
physical examination. Regarding symptoms, the
presence of a new headache is frequent in CVST,
SAH, and some strokes related to vasculitis. A
sudden onset of a focal deficit is usually correlated
with an embolic or atherosclerotic cause. Seizures
can be present in any of these conditions, but are
probably more frequent in cases related to
vasculitis.
During the physical examination, a careful
search for systemic signs related to disease activity
must be sought (e.g. dermatological features, arth-
ritis, serositis, livedo reticularis). The neurological
exam must include the level of consciousness deter-
mination, language testing, strength, reflexes, sens-
ibility, cranial nerves, coordination, and balance.
The NIHSS is a good guide for the gross evaluation
of these patients and is mandatory when a sudden
deficit is being evaluated.21