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Sjogren's syndrome presenting as ischemic

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Article in Stroke December 1994

DOI: 10.1161/01.STR.25.11.2276 Source: PubMed

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 Sjogren's syndrome presenting as ischemic stroke
M Bragoni, V Di Piero, R Priori, G Valesini and GL Lenzi

Stroke 1994, 25:2276-2279

Stroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514
Copyright 1994 American Heart Association. All rights reserved. Print ISSN: 0039-2499. Online ISSN:
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2276
Case Reports
Sjogren's Syndrome Presenting
as Ischemic Stroke
M. Bragoni, MD; V. Di Piero, PhD; R. Priori, MD; G. Valesini, MD; G.L. Lenzi, MD
Background We describe a young woman who presented
with minor stroke as a first clinical symptom of Sjogren's
syndrome (SS) in the absence of well-known risk factors for
cerebrovascular disease.
Case Description The medical history included recurrent
miscarriages and sun rashes, which directed the diagnosis
toward inununologic disorders such as systemic lupus erythe-
matosus and antiphospholipid antibody syndrome, which are
S jogren's syndrome (SS) is an autoimmune disease
characterized by focal or confluent lymphocytic
infiltrates in the exocrine glands; the main clin-
ical symptoms are dry eyes and xerostomia.1 Females
are affected more frequently than males.
The psychiatric and neurological complications of SS
have been described.2 Peripheral nervous system (PNS)
complications are more common than central nervous
system (CNS) complications.3-4 CNS complications oc-
cur in approximately 25% of patients, usually late in the
course of the disease.1-3-5'6 Few patients have been
described with CNS or PNS symptoms as the first
clinical presentation of SS,7 but an embolic stroke
associated with cardiomyopathy has been described as
the first clinical presentation.8
We describe a patient with minor stroke as the
presenting feature of SS; no other risk factors for stroke
were identified.
Case Report
A 44-year-old woman was admitted to our unit with
mild weakness of the right arm, concentration and
memory difficulties, and a recent onset of xerostomia.
Four months earlier she had presented with a sudden
onset of confusion, speech problems, weakness, and
sensory loss of the right arm. The confusion subsided in
a few hours, and the other symptoms subsided within 48
hours. At that time a computed tomographic scan of the
brain, a carotid ultrasound, and cerebral angiography
were normal. A transient ischemic attack was diagnosed
at that time.
Her medical history included three miscarriages,
headaches, a facial rash when exposed to the sun, and
Received March 10, 1994; final revision received July 15, 1994;
accepted July 29, 1994.
From V Clinica Neurologica (M.B., V. Di P., G.L.L.) and I
Clinica Medica (R.P., G.V.), Universita' di Roma "La Sapienza,"
Rome, Italy.
Correspondence to Maura Bragoni, MD, Department of Neu-
rosciences, V Clinica Neurologica, V le dell'Universita' 30, 00185,
Rome, Italy.
O 1994 American Heart Association, Inc.
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often associated with stroke. Only complete laboratory testing,
including SSB antibody studies, and ophthalmologic and sali-
vary gland evaluation revealed the correct diagnosis.
Conclusions SjSgren's syndrome should be considered
among the causes of stroke, especially in a young female
patient. (Stroke. 1994^5:2276-2279.)
Key Words risk factors Sjflgren's syndrome young
adults cerebrovascular disorders
arthralgia for several years. No other risk factors such as
hypertension, diabetes, smoking, contraceptive drug
use, or family or personal history of thromboses were
present.
The physical general examination revealed patches of
skin depigmentation in both arms, a small thyroid
nodule, and a cardiac systolic murmur. The neurological
examination was normal except for weakness, hyperre-
flexia, and hypoesthesia of the right arm. An extensive
neuropsychological assessment revealed mild impair-
ment in regard to attention and visuospatial problems,
long-term verbal memory deficits, and word-finding
problems.
Routine laboratory tests were all normal except for
erythrocyte sedimentation rate (15; normal, <10), hy-
pergammaglobulinemia (25%; normal, 12% to 20%),
slight serum IgG increase (1430 mg/dL; normal range,
700 to 1350 mg/dL), and hypocholesterolemia (130
mg/dL; normal range, 160 to 240 mg/dL).
Other laboratory testing revealed the presence of
antinuclear antibodies, as shown by indirect immuno-
fluorescence on human epithelial cells (pattern coarse
speckled, standard serum dilution 1/40) and anti-SSB
antibodies (counterimmunoelectrophoresis and West-
ern blotting). Anti-DNA antibodies and other anti-
extractable nuclear antigens (anti-SSA, anti-Smith,
anti-scleroderma 70), lupus anticoagulant, anticardio-
lipin antibodies, rheumatoid factor, cryoglobulins, and
circulating immune complexes were negative. A plate-
let aggregation study and fibrinogen level were nor-
mal. The plasma levels of inhibitory coagulation factor
proteins such as antithrombin III, protein C, and
protein S were normal.
A standard electrocardiogram and 24-hour Holter
electrocardiogram were normal. Transthoracic and
transesophageal echocardiography revealed thickening
of the mitral valve associated with a mild tricuspid
insufficiency. Somatosensory evoked potentials, brain
stem auditory evoked potentials, electroencephalo-
gram, and nerve conduction velocities were in the
normal range. A brain computed tomographic scan was
normal; however, magnetic resonance imaging (MRI)
 Bragoni et al Sjogren's Syndrome and Ischemic Stroke 2277

Magnetic resonance images show two areas of hyperintensity on T r welghted image (right panel) and corresponding hypointenstty on
T,-weighted image (left paneO In the territory of the left middle cerebral artery, involving the cortex of the insuia and the giobus paiiidum.
R indicates right; L, left.

showed two areas of hyperintensity on T2-weighted
images and corresponding hypointensity on T r weighted
images in the territory of the left middle cerebral artery,
involving the cortex of the insuia and the giobus paiii-
dum (Figure).
An ophthalmologic examination revealed an abnor-
mal break time and a rose bengal score greater than 4,
diagnostic of keratoconjunctivitis sicca.9 Minor salivary
gland biopsy revealed more than one focus of lympho-
cytes in 4 mm2 of tissue, thus determining a grade IV
lymphocytic adenitis according to the Chishol-Mason
scale and confirming the diagnosis of SS.10
The patient was treated with steroid and immunosup-
pressive therapy (dexamethasone, 20 mg once a week,
and methotrexate, 7.5 mg once a week). In the following
months she also presented with an autoimmune thy-
roiditis, which improved after adequate therapy. We
continued to follow up the patient for more than 2
years, and she did not present with any other cerebral
ischemic symptoms.
Discussion
In this patient the onset and time course of the
neurological symptoms as well as the MRI findings
suggest the occurrence of a minor stroke in the vascular
territory of the left middle cerebral artery.
Normal carotid duplex scan and cerebral angiography
ruled out disease of the extracranial and intracranial
large arteries as a possible cause of stroke. A possible
cardioembolic mechanism was considered, but transtho-
racic and transesophageal echocardiography ruled out
the presence of relevant cardiac and aortic abnormali-
ties. The only detectable cardiac abnormality was thick-
ening of the mitral valves, which is not in itself consid-
ered an independent risk factor for cardiac embolism to
the brain.11 Additionally, Hess12 found that only the
combination of antiphospholipid antibodies and mitral
valve abnormalities was associated with brain embolism.
In our patient antiphospholipid antibodies were nega-
tive on more than one occasion. Finally, we did not find
any detectable cardiac arrhythmias.
Because of her young age and the absence of vascular
and cardiac risk factors for cerebrovascular disease,
hematologic and immunologic abnormalities were con-
sidered in the etiopathogenesis of the stroke. A congen-
ital or acquired deficiency of inhibitory coagulation
factor proteins such as antithrombin III, protein C, and
protein S, which has been established as probable cause
of ischemic stroke in both young and old patients,1314
was ruled out. Possible immunologic abnormalities were
then considered. The clinical clues that alerted us to the
presence of an underlying immunologic disorder were
the presence of three miscarriages and sun rashes in her
medical history. The possibilities of antiphospholipid
antibody syndrome and systemic lupus erythematosus,
often associated with stroke,1516 were considered. Our
patient did not fulfill established criteria for systemic
lupus erythematosus or for antiphospholipid antibody
syndrome. On the other hand, the presence of antinu-
clear antibodies and anti-SSB antibodies, a quite spe-
cific marker for SS,17-18 led us to perform more thorough
testing for SS. The ophthalmologic testing and the
salivary gland biopsy confirmed the diagnosis of SS,
according to the criteria of the most recent classification
of SS.17 Moreover, the association with autoimmune
thyroiditis and vitiligo frequently described in SS, a

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2278 Stroke Vol 25, No 11 November 1994
well-known polyglandular (exocrine and endocrine) au-
toimmune disease,19 completed the clinical presentation
in our patient.
Approximately 25% of SS patients present with CNS
complications3-3-6 and approximately 10% to 20% with
PNS complications.3 The entire neuroaxis, the periph-
eral and cranial nerves, and the ganglia may be involved
during SS. A neurological presentation of SS is consid-
ered unusual in either the PNS 2023 or the CNS.3 A
stroke as first clinical presentation of SS has been
described in association with cardiomyopathy,8 but this
was not true in our case. This is the first well-docu-
mented large-artery minor stroke occurring in a young
woman in whom no cause other than uncomplicated SS
has been found.
The etiopathogenesis of the neurological damage in
SS seems to be immunologically mediated. The most
common mechanism of PNS and CNS involvement
during SS is due to vasculitis of small vessels. Necrotiz-
ing vasculitis24-25 involving the entire neuroaxis has been
described in two autopsied cases of SS. T- and B-lym-
phocytic perivascular leptomeningeal and intraparen-
chymal infiltration is described in a brain biopsy in a
case of reversible dementia associated with SS.2* A vasa
nervorum vasculitis with monocytic,27 rymphocytic,3 and
neutrophilic3 infiltration has been described in associa-
tion with clinical symptoms of polyneuropathy in SS
patients. Antimyelin autoantibodies have also been de-
scribed for PNS complications28 during SS. On the other
hand, Grauss et al21 did not find signs of vasculitis or
autoantibodies against myelin in patients affected by
sensory neuropathy, suggesting another possible cellu-
lar-mediated mechanism.
According to Alexander,3 brain autopsies in SS pa-
tients who died in association with severe CNS compli-
cations showed minute microhemorrhages and/or mi-
croinfarcts associated with extensive small parenchymal
endothelial damage secondary to a few mononuclear
perivascular inflammations. According to the author,
this type of vasculopathy would be progressive and
cause clinical symptomatology only when larger lesions
involve a clinically critical region of the brain.
No more than 20% of patients affected by SS have
abnormal cerebral angiography suggestive of brain vas-
culitis.3 In our patient normal cerebral angiography
ruled out the presence of extracranial and intracranial
arterial diseases but gave us limited information about
possible small-vessel disease. Brain biopsy, potentially
diagnostic for inflammatory disease or small-vessel vas-
culitis, was refused by the patient.
CNS involvement during SS may be studied noninva-
srvely with MRI. This seems to be the most sensitive
among thenoninvasive tests for SS, being able to detect
lesions in more than 75% of patients, whereas com-
puted tomographic scan of the brain is positive in only
20% of patients.6 MRI abnormalities may include areas
of increased signal intensity on T2-weighted images and
decreased signal intensity on the corresponding T r
weighted images. The lesions may be located in the
periventricular deep white matter and less frequently in
the gray matter. In our patient the involvement of the
gray matter of insula and globus pallidum was demon-
strated by the MRI.
In our patient the stroke represented the clinical
onset of SS. Only a thorough exclusion of other common
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causes of stroke and a complete hematologic and im-
munologic screening for disorders rarely associated with
cerebrovascular disease revealed the diagnosis.
In conclusion, we believe that young stroke patients
without well-known risk factors for stroke should also
be evaluated for SS, even in the absence of other
clinical symptomatology. The laboratory screening
should include immunologic tests such as antinuclear
antibodies and anti-SSB and/or anti-SSA antibodies;
ophthalmologic and salivary gland evaluation should
be performed only if the immunologic screening for SS
is positive.
Acknowledgments
The authors wish to thank Dr Patrizia Franco for the
neuropsychological evaluation of the patient and Janet Wilter-
dink, MD, and Edward Feldmann, MD, for their comments on
an earlier draft.
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