Service de Neurology
Service de Hematology,
University Hospital Marqués de Valdecilla,
Faculty of Medicine,
Santander, Spain
To the Editor:
The presence of Down's syndrome (DS) associated with moyamoya
disease has been increasingly noted in the last years. Several reports
suggest that the incidence of moyamoya disease is higher in
children with DS than in other children. Since 1977, when this
association was described for the first time, more than twenty cases
have been reported.1 2 3 However, the reason of
this association is unknown. Furthermore, DS is associated with
autoimmune disorders.4 We describe a child with
trisomy 21 affected by moyamoya and Graves' disease, associated
with anti-thyroid microsome antibodies and antiphospholipid antibodies
(aPL). This patient was included in the prospective study of stroke in
young adults in Cantabria, Spain.5 6
A 21-year-old man was admitted to the hospital on May 27, 1986.
Thirteen days before, his mother noticed a sudden muscle weakness in
his left arm; 3 days later she also noted that he had difficulty in
walking because of a weakness in his left leg. The patient was the
eighth pregnancy of a mother who was 39 years of age at the time of
delivery. When he was a baby, a mental deficiency was noted, and he
also suffered from an incomplete acquisition of the language, with use
only of monosyllables.
His blood pressure was 110/50 mm Hg and his pulse was 130. On
general physical examination a mongoloid face, bilateral exophthalmos,
and diffuse goiter were present. On neurological examination a
moderate left hemiparesis with increased deep tendon reflexes of the
left extremities was found.
Except for an increase of serum gamma globulin (23%), routine
laboratory investigations were normal. A serologic test for syphilis
and tests for antinuclear antibodies were negative. A lumbar puncture
yielded normal cerebrospinal fluid. A x-ray examination of chest showed
no abnormalities. An ECG and 24-hour Holter monitoring revealed sinus
tachycardia at a rate of 130. An
echocardiographic study demonstrated hyperdynamic
systolic left ventricular function. A diagnosis of
trisomy 21, clinically suspected, was confirmed by karyotyping.
Thyroid function tests showed the total thyroxine 21.2 µg/dL (normal
value, 4.0 to 12.5), the total T3 583
A CT scan of the cranial contents demonstrated a septum pellucidum
cyst, slight calcifications in the basal ganglia, and right
paraventricular frontal infarct. Right vertebral and
internal carotid angiography showed marked stenosis of the
supraclinoid portion of the carotid artery, important decreased flow in
the middle cerebral artery, and nonvisualization of the anterior
cerebral artery. Lenticulostriate arteries were prominently shown. The
vertebrobasilar territory was normal, and there was a transcortical
anastomosis from posterior cerebral arteries to anterior cerebral
arteries. Left internal carotid angiography demonstrated a very poor
visualization of anterior cerebral arteries.
A diagnosis of DS, Graves' disease, and moyamoya disease was
established. The patient was treated with antithyroid agents and 250 mg
acetylsalicylic acid daily. As a result of the
cerebral infarction, the patient suffered a moderate disability in his
left limbs. Antithyroid treatment was stopped in 1991; however, thyroid
function continued to be normal from that point. Neither other
cerebrovascular disorders nor other major diseases have since been
detected in the patient. The last laboratory exams, which were carried
out in January and August 1997, showed slight positive LA, positive ACA
ELISA test (50 UGPL/mL), positive antimicrosomal antibodies (1:1000),
and serum hypergammaglobulinemia of 31%.
This patient was diagnosed of Graves' disease and presence of thyroid
autoantibodies. Patients with DS are known to have an altered immune
system. In particular, they have an increased prevalence of autoimmune
disorders, such as autoimmune thyroid disease.4
The high prevalence of thyroid autoantibodies found in DS patients
(39.3%)4 supports the recognized association
between thyroid dysfunction and DS.
Our patient also had aPL. The report of a woman with autoimmune
hyperthyroidism and the presence of LA, antimicrosomal antibodies, and
ACA has been described.7 Also reported has been
the case of a child with trisomy 21 affected by hypothyroidism
associated with antithyroglobulin and anti-thyroid microsome antibodies
in the blood.8 Moreover, this patient was
affected by multiple arterial thromboses in association
with ACA, thus suggesting the antiphospholipid
syndrome.8 This observed association does not
seem a casual fact: on the contrary, it would possibly be related to
unknown exogenous factors acting on subjects genetically predisposed to
autoimmunity.8
Furthermore, our DS patient had clinical and radiological features
consistent with the diagnosis of moyamoya disease. At
present, the etiology of this disease is still unknown. It is not
clear whether moyamoya disease represents a congenital
arterial displasia or is a syndrome caused by nonspecific
vascular reaction. Recently, it has been postulated that a protein
encoded on chromosome 21 may be related to the pathogenesis of
moyamoya disease.1 However, the presence in
trisomy 21 patients of autoimmune processes and autoantibodies make us
suspect that the higher frequency of moyamoya disease in DS could
be also result from an immune disturbance. Moreover,
moyamoya disease itself has been associated with
aPL.9
We conclude that different autoantibodies may be produced in DS. In
subjects genetically predisposed to autoimmunity, these or other
unknown antibodies could be associated with moyamoya disease. We
believe that testing for plasma aPL is important in DS associated with
moyamoya disease.
References
1.
Cramer SC, Robertson RL, Dooling EC,
Scott RM. Moyamoya and Down syndrome: clinical and radiological
features. Stroke. 1996;27:2131–2135.
2.
Fukuyama Y, Osawa M, Kanai N. Moyamoya disease
(syndrome) and the Down syndrome. Brain Dev. 1992;14:254–256.[Medline]
[Order article via Infotrieve]
3.
Schrager GO, Cohen SJ, Vigman MP. Acute hemiplegia and
cortical blindness due to Moyamoya disease: report of a case in a
child with Down's syndrome. Pediatrics. 1977;60:33–37.
4.
Friedman DL, Kastner T, Pond WS, O'Brien DR. Thyroid
dysfunction in individuals with Down syndrome. Arch Intern
Med. 1989;149:1990–1993.
5.
Leno C, Berciano J, Combarros O, Polo JM, Pascual J,
Quintana F, Merino J, Sedano C, Martín-Durán R, Alvarez
C, Llorca J. A prospective study of stroke in young adults in
Cantabria, Spain. Stroke. 1993;24:792–795.
6.
Leno C, Berciano J, Combarros O, Sedano C, Alvarez C,
Merino J, Quintana F, Martín-Durán R, Rebollo M, Pascual
J, Polo JM. Etiologic study of stroke in 95 young adults.
Neurología. 1995;10:283–287.
7.
Schuler G, Alexopoulos A, Hasler K, Kerp L.
Lupus-Antikoagulans bei immunhyperthyreose. Dtsch Med
Wschr. 1990;115:1511–1514.[Medline]
[Order article via Infotrieve]
8.
Guariso G, Ruffatti A, Casonato A, Drigo P,
Ghirardello A, Zancan L. Antiphospholipid syndrome in a child with
trisomy 21: the relationship between anticardiolipin G antibodies and
the von Willebrand factor. Clin Exp Rheumatol. 1992;10:613–616.[Medline]
[Order article via Infotrieve]
9.
Fujiwara S, Miyazono M, Tsuda H, Fukui M.
Intraventricular hemorrhage and cerebral
ischemic attacks in the presence of lupus anticoagulant
mimicking Moyamoya disease. J Neurosurg Sci. 1993;37:161–164.[Medline]
[Order article via Infotrieve]
© 1998 American Heart Association, Inc.
Letters to the Editor
Autoimmunity in Down's Syndrome: Another Possible Mechanism of Moyamoya Disease
g/dL (80
to 210), the resin T3 uptake index 1.34 (0.85 to 1.15), the thyrotropin
<0.5 mUI/L (0.15 to 4.5), negative antithyroglobulin antibodies, and
positive antimicrosomal antibodies (titer of 1:400). The thyroid
scintigraphy with 99mTc demonstrated
a thyroid gland uniformly increased in size, with a regular
distribution of the tracer. The coagulation studies revealed slight
positive lupus anticoagulant (LA). Positive IgG anticardiolipin
antibodies (ACA) were disclosed in plasma.
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