Journal of the Neurological Sciences 163 (1999) 86–89

Localized scleroderma associated with progressing ischemic stroke
a,

b

c

b

b

Naomi Kanzato *, Toshio Matsuzaki , Yukihiro Komine , Mineki Saito , Akiko Saito ,
Taku Yoshio d , Masahito Suehara a
a

Department of Neurology, National Okinawa Hospital, Ganeko 3 -20 -14, Ginowan-shi, Okinawa 901 -2214, Japan
b
Third Department of Internal Medicine, Kagoshima University, Kagoshima, Japan
c
Third Department of Internal Medicine, Ryukyus University, Okinawa, Japan
d
Department of Clinical Immunology, Jichi Medical School, Jichi, Japan
Received 30 March 1998; received in revised form 14 August 1998; accepted 14 August 1998

Abstract
We present a 73 year-old Japanese woman with localized scleroderma involving the right side of the scalp accompanied by continuous
tingling pain, who developed insidiously progressive left hemiparesis. In magnetic resonance imaging of the brain, an infarct first
appeared in the watershed region of the right middle cerebral artery territory and subsequently extended to deep white matter accompanied
by scattered hemorrhages. Focal stenosis in the M2 portion of the right middle cerebral artery was revealed on magnetic resonance
angiography, and the distal vessels were only shown faintly. A biopsy specimen from the sclerotic scalp lesion showed obvious thickening
of vessel walls and mild mononuclear cell infiltration. We believe that the progressing ischemic stroke was caused by hemodynamic
disturbances from localized sclerotic obstruction of the middle cerebral artery, with an autoimmune pathogenesis.  1999 Published by
Elsevier Science B.V. All rights reserved.
Keywords: Localized scleroderma; Cerebral infarction; Central nervous system vasculitis; Anti-endothelial cell antibody

1. Introduction
Systemic sclerosis (SS), a progressive multiorgan disorder, involves mainly the skin, joints, lungs, heart and
kidneys, as well as other sites. Localized scleroderma (LS)
is confined to the skin. In both SS and LS, primary
sclerodermal involvement of cerebral vessels is exceedingly rare, possibly due to the paucity of adventitial fibrous
tissues and limited fibrous elements in the normal media
[7]. Only a few reports have described the histopathology
of cerebral arteries in LS [5,9]; these have noted thickened
sclerotic vessel walls but no vascular inflammation or
fibrinoid degeneration.

*Corresponding author. Tel.: 181-98-898-2121; fax: 181-98-8979838.

We describe an elderly woman with sclerotic scalp and
associated pain who insidiously developed hemiparesis.
This ischemic stroke progressed over a few months,
accompanied by foci of hemorrhage.

2. Case report
A 73 year-old, right-handed Japanese woman insidiously
developed severe tingling pain, erythema and hair loss
over the right side of the scalp from September 1995. She
noted mild paresis in her left arm from November, then
came to our outpatient clinic. We confirmed these findings,
but magnetic resonance imaging (MRI) of the brain and
cervical spinal cord were not contributory. By January
1996 she had developed complete palsy of the left arm
with arthralgia and edema, and also mild paresis in the left

0022-510X / 99 / $ – see front matter  1999 Published by Elsevier Science B.V. All rights reserved.
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N. Kanzato et al. / Journal of the Neurological Sciences 163 (1999) 86 – 89

leg. On admission in February, she had left supranuclear
facial paresis.
On admission, she was alert and normotensive, with
normal cardiac rhythm and body temperature. A regional
sclerotic skin lesion accompanied by erythema and hair
loss was noted extending from the right forehead to the
parietal scalp (Fig. 1), where the patient felt continuous
tingling pain. No swelling or tenderness over the temporal
artery was apparent. Examination of the eye was normal,
and no bruit was evident on the neck. Diffuse hyperpigmentation was noted over her trunk and extremities. Left
hemiparesis including her left face was noted. In her
paralyzed left arm, dysesthesia and painful joints with
swelling and increased skin temperature were noted, which
were considered to be shoulder-hand syndrome. Deep
tendon reflexes were brisk except for the right arm. No
pathologic reflexes were seen.
Results of routine hematologic and other laboratory tests
showed eosinophilia (1360 / mm 3 ; normal ,500 / mm 3 ),
decreased platelets (3.0310 4 / ml; normal 15–40310 4 / ml),
slightly increased erythrocyte sedimentation rate, and
elevated C-reactive protein. Elevated serum IgA (1090
mg / dl; normal 115–440 mg / dl) was evident, but an M
protein was not detected. Anti-topoisomerase I antibody
(Scl-70) was elevated slightly, and antinuclear antibody
showed a speckled pattern. Antimitochondrial antibody
was markedly increased (.320; normal ,20) with a
nonspecific immunofluorescence pattern, but the antimitochondrial M2 antibody was negative. A serologic test
for syphilis was negative. Coagulation tests including
activated partial thromboplastin time (APTT) and levels of
antithrombin III (AT III) were normal. Tests for lupus
anticoagulant and anticardiolipin antibody were negative.

Fig. 1. Bandlike sclerotic lesion with erythema and hair loss extending
from the right forehead to the parietal scalp.

87

Other serum biochemical tests and a urinalysis were all
normal. Cerebrospinal fluid (CSF) examination revealed a
slightly elevated opening pressure (225 mm H 2 O) and
myelin basic protein (4.9 ng / ml; normal ,4 ng / ml), but
other constituents such as cells and protein were normal.
Oligoclonal IgG bands were not detected. Bone marrow
findings included a slightly elevated proportion of plasma
cells (3.7%, normal 0.3–1.5%). No pulmonary fibrosis was
seen in radiographs of the chest, and no intracardiac
thrombosis was evident in the echocardiogram. Electroencephalography, nerve conduction, and needle EMG
were normal.
Anti-endothelial cell antibodies (AECA) were examined
by cellular ELISA methods [11] using an antigen from
cultured human vein endothelial cells (HUVEC). The
patient’s serum contained normal levels of both the IgMAECA and IgG-AECA, the CSF contained significantly
elevated levels of IgM-AECA (16.5 CSF unit / ml; normal,
0.860.7) and IgG-AECA (5.8 CSF unit / ml; normal,
1.160.9).
In a biopsy specimen from the right parietal scalp
involving LS, erosive change with loss of epidermis was
noted, together with swelling of connective tissues. Arteriolar lumens were narrowed by mural thickening with
excessive numbers of collagen fibers. Mild mononuclear
cell infiltration was present without amyloid deposition
(Fig. 2).
MRI of the brain repeated on admission revealed lesions
with high signal intensity in the right middle cerebral
artery (MCA) territory, especially in the watershed region,
in T2- and proton-weighted images (Fig. 3a). In T1weighted images, multiple enhancements were evident
within the cortical branches and the lenticulostriate branch
of MCA by administration of gadolinium-DTPA (Fig.
3b,c). Magnetic resonance angiography (MRA) revealed
focal stenosis at the insular portion (M2) of the right

Fig. 2. Arteriolar lumens were narrowed by mural thickening with
excessive numbers of collagen fibers accompanying mild mononuclear
cell infiltration (Masson trichrome stain, 340).

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N. Kanzato et al. / Journal of the Neurological Sciences 163 (1999) 86 – 89

Fig. 3. MRI and MRA in February 1996: (a) proton-weighted (TR 2000 / TE 40); (b) and (c) Gd-DTPA T1-weighted (TE 500 / TE 20) image of spin echo
sequences; (d) MRA. Ischemic changes were evident at the watershed region of the right MCA. Gd-enhancements were apparent within the region of
cortical branches and lenticulostriate branch (n) of right MCA. MRA revealed focal stenosis of the M2 insular portion of the right MCA (→), and obscure
images of distal arteries.

MCA, and the distal arteries were poorly visualized (Fig.
3d).
We carried out hypervolemic hemodilution for the
therapy of hemodynamic ischemia [1] with low molecular
weight dextran solution for 2 weeks, but the head pain and
left hemiparesis continued. Then we followed with oral
prednisolone (30 mg / day) and intramuscular dexamethasone (1 mg / day) administration for 1 month, which
relieved the paresis of the left face and leg, concurrently
with the disappearance of continuous head pain and LS of
the scalp. MRI of the brain was conducted after a course of
steroid therapy, T2- and proton-weighted images showed
an extensive lesion of high signal intensity in the deep
white matter of the right MCA territory, accompanied by
old scattered hemorrhages with low intensity. In conjunction with these findings, T1-weighted images revealed
linear lesions of high intensity just beneath the cortex (Fig.
4a,b).
We treated her shoulder–hand syndrome with stellate
ganglion blockade weekly for 4 weeks, and her joint pain
and edema markedly decreased, although the paresis of the
left arm accompanied with joint contractures in a Wernicke-Mann posture remained.

3. Discussion
The patient was diagnosed with LS based on the
findings of a characteristic sclerotic lesion of the scalp [8],
diffuse hyperpigmentation, and serum autoantibodies associated with scleroderma, but without visceral involvement.
Her left hemiparesis appeared insidiously and evolved
over a few months. MRA findings of this case lacked the
disease specificity for vasculitis, we could not distinguish
it from the atherosclerotic lesion based solely on these
findings [6]. However, MRI findings failed to show
common atherosclerotic thrombosis or embolism, because
of the insidious evolution of the infarct from the watershed
region to the deep white matter accompanied by scattered
enhancements and hemorrhages within the right MCA
territory. We concluded that this atypically progressing
ischemic stroke was most likely caused by a progressive
hemodynamic process, arising from vulnerability to low
perfusion at the proximal stenotic region demonstrated by
MRA.
AECA have been demonstrated in serum as a pathogenesis of vasculitic organ damage in some connective
tissue disease such as systemic lupus erythematosus and

N. Kanzato et al. / Journal of the Neurological Sciences 163 (1999) 86 – 89

89

Fig. 4. MRI after the corticosteroid therapy in April 1996: (a) proton-weighted; (b) non-enhanced T1-weighted image. A high-intensity lesion had evolved
to the deep white matter within the right MAC territory, in conjunction with old scattered hemorrhages of low intensity. T1-weighted images revealed
linear intensity lesions just beneath the cortex.

SS [2]. Intrathecal AECA production was demonstrated in
our case for the first time in LS, which supported an
autoimmune pathogenesis of cerebrovascular injury in this
case.
Most curiously, the ischemic cerebral infarction in this
case occurred just subjacent to the LS lesion of the scalp.
¨ et al. [10] postulated that
Chung et al. [5] and Luer
vascular dysgenesis may be underlying in the progressive
gliosis of cerebral parenchyma just under an LS scalp
lesion. Endothelial cell damage is believed to be the
primary event in LS [3], following fibrotic change triggered by disordered regulation of genes affecting collagen
formation [4]. LS is much less severe and carries a more
favorable prognosis than SS, but associated vascular events
may limit the functional outcome. Better understanding of
the pathogenesis of LS should facilitate the tailoring of
therapy in response to key events in the evolution of the
disease.

References
[1] Adams HP, Brott TG, Crowell RM. Guidelines for the management
of patients with acute ischemic stroke. Circulation 1994;90:1588–
601.

[2] Baguley E, Hughes GRV. Antiendothelial call antibodies. J
Rheumatol 1989;16:716–7.
[3] Black CM. The aetiopathogenesis of systemic sclerosis. J Int Med
1993;234:3–8.
[4] Black CM, Denton CP, Korn JH, Crombrugghe B. Systemic
sclerosis: Current pathogenetic concepts and future prospects for
targeted therapy. Lancet 1996;347:1453–8.
[5] Chung MH, Sum J, Morrell MJ, Horoupian DS. Intracerebral
involvement in scleroderma en coup de sabre: Report of a case with
neuropathological findings. Ann Neurol 1995;37:679–81.
[6] Fieschi C, Rasura M, Anzini A, Beccia M. Central nervous system
vasculitis. J Neurol Sci 1998;153:159–71.
[7] Gordon RM, Silverstein A. Neurologic manifestations in progressive
systemic sclerosis. Arch Neurol 1970;22:126–34.
[8] Jablonska S, Lovell CR. Localized scleroderma. In: Jayson MIV,
Black CM (Eds.), Systemic Sclerosis: Scleroderma, Wiley: Chichester, 1988:303–318.
[9] Lee JE, Haynes JM. Carotid arteritis and cerebral infarction due to
scleroderma. Neurology 1967;17:18–22.
¨ W, Jockel D, Henze T, Schipper HI. Progressive inflammatory
[10] Luer
lesions of the brain parenchyma in localized scleroderma of the
head. J Neurol 1990;237:379–81.
[11] Yoshio T, Masuyama J, Sumiya M, Minota S, Kano S. Antiendothelial cell antibodies and their relation to pulmonary hypertension in systemic lupus erythematosus. J Rheumatol 1994;21:2058–
63.