Brazilian Journal of Medical and Biological Research (2002) 35: 431-436 431
Brain SPECT in Sydenham’s chorea
Brain SPECT imaging in
O.G.P. Barsottini1, 1Setorde Distúrbios do Movimento, Departamento de Neurologia and
H.B. Ferraz1, M.M. Seviliano2 2Setorde Medicina Nuclear, Departamento de Diagnóstico por Imagem,
and A. Barbieri2 Universidade Federal de São Paulo, São Paulo, SP, Brasil
Correspondence The objective of the present study was to determine whether brain Key words
H.B. Ferraz single-photon emission computed tomography (SPECT) imaging is · Sydenham’s chorea
Al. Casa Branca, 799, Apto. 72 capable of detecting perfusional abnormalities. Ten Sydenhams cho- · Single-photon emission
01408-001 São Paulo, SP
rea (SC) patients, eight females and two males, 8 to 25 years of age computed tomography
Brasil · SPECT imaging
(mean 13.4), with a clinical diagnosis of SC were submitted to brain
· Rheumatic fever
E-mail: firstname.lastname@example.org SPECT imaging. We used HMPAO labeled with technetium-99m at a
· Brain perfusion
dose of 740 MBq. Six examinations revealed hyperperfusion of the
Publication supported by FAPESP. basal ganglia, while the remaining four were normal. The six patients
with abnormal results were females and their data were not correlated
with severity of symptoms. Patients with abnormal brain SPECT had
a more recent onset of symptoms (mean of 49 days) compared to those
Received April 6, 2001
with normal SPECT (mean of 85 days) but this difference did not reach
Accepted January 28, 2002
statistical significance. Brain SPECT can be a helpful method to
determine abnormalities of the basal ganglia in SC patients but further
studies on a larger number of patients are needed in order to detect the
phase of the disease during which the examination is more sensitive.
Introduction genesis of the disease by producing antibod-
ies against the subthalamic and caudate nu-
Sydenhams chorea (SC) has been known clei (6). High levels of IgG are found in
since the middle ages, but its relationship cerebrospinal fluid during the acute phase of
with rheumatic fever was established only in the disease (7).
the 19th century (1). According to Jones The number of streptococcal infections is
criteria (2), it is currently considered as a much higher than the number of patients
major manifestation of rheumatic fever. In with rheumatic fever. Rheumatic fever, on
80% of cases, SC mainly affects children and the other hand, involves a much higher num-
adolescents, although occurrence in young ber of patients with clinical abnormalities
adults is not rare (3,4). other than choreic movements. It is currently
In 1948 a relationship was established believed that the presence of streptococcal
between rheumatic fever and the infection toxins may induce patient sensitivity and
caused by the beta-hemolytic streptococcus that, depending on genetic and environmen-
of group A (5). There is also evidence that tal factors, patients may develop the symp-
the immune system plays a role in the patho- toms of rheumatic fever.
Braz J Med Biol Res 35(4) 2002
432 O.G.P. Barsottini et al.
The diagnosis of SC is not easy since the tients with the diagnosis of SC and to corre-
streptococcal infection is difficult to iden- late the clinical findings with the results.
tify, especially because many times there is
no association with other manifestations of Patients and Methods
rheumatic fever. In about 20 to 25% of the
acute chorea cases, no laboratory or clinical Ten patients were selected from the Out-
evidence of previous rheumatic disease could patients Clinic of the Movement Disorders
be found (4). Also, the time between strepto- Unit, Department of Neurology, Federal
coccal infection and the onset of chorea may University of São Paulo, São Paulo, SP,
be long, resulting in negative laboratory tests Brazil. There were 8 female and 2 male
which might not confirm the rheumatic patients with a mean age of 13.4 years (age
state (4). Thus, the diagnosis of SC is largely range 8 to 25 years).
presumptive, based merely on the clinical The study was submitted to and approved
manifestations of chorea in young patients by the Ethics Research Committee of São
without evidence of other causes. Paulo Hospital, Federal University of São
Some clinical and laboratory data are Paulo. Patients or their parents were informed
especially useful to establish the diagnosis about benefits and risks of the procedure and
of SC. Clinical data include the presence of gave written informed consent to participate
involuntary movements of insidious onset, in the study.
absence of a family history of abnormal Inclusion criteria were the presence of
movements, and absence of drug use before choreic movements with onset within the
or during the onset of abnormal movements. last 6 months, and age from 5 to 25 years.
The laboratory findings include normal thy- Exclusion criteria were presence of other
roid, renal or hepatic function, normal ceru- neurological manifestations unrelated to cho-
loplasmin levels, negative tests for the rheu- rea, such as cognitive impairment and ataxia;
matoid factor and antinuclear antibodies, and past history of perinatal trauma; family his-
normal red cell count (8). tory of abnormal movements, except for SC;
Single-photon emission computed tomog- presence of thyroid, renal, hepatic or psychi-
raphy (SPECT) depicting regional cerebral atric diseases preceding or accompanying
perfusion could be a useful method to evalu- the abnormal movements; use of drugs known
ate basal ganglion function. Preliminary stud- to cause chorea (i.e., neuroleptics, levodopa,
ies show hypoperfusion (hypoconcentration) phenytoin) preceding or accompanying the
in degenerative choreas and hyperperfusion abnormal movements, and a history of sys-
in infectious choreas, such as SC (9,10). temic lupus erythematosus.
SPECT was introduced at the beginning of Patients did not need to fulfill criteria for
the 80s and has permitted the assessment of the diagnosis of rheumatic fever in order to
regional cerebral perfusion. One of its ad- be included in the study; however, the pres-
vantages resides in the low cost of the exami- ence of signs and symptoms of rheumatic
nation when compared to other techniques fever was decisive for the diagnosis of SC in
of functional analysis of the brain. In SC the case of doubt.
number of cases studied by this method is All patients were submitted to clinical
small and conclusions about the value of examination and to a minimum protocol of
SPECT in the investigation of patients are laboratory tests which included complete
not very clear. blood count, erythrocyte sedimentation rate,
Our objective was to determine whether antistreptolysin O, chest X-ray, and electro-
brain SPECT imaging is capable of detecting cardiogram.
perfusional abnormalities in a group of pa- Complementary examinations, such as
Braz J Med Biol Res 35(4) 2002
Brain SPECT in Sydenham’s chorea 433
thyroid tests, ceruloplasmin or urinary cop- ing the cerebellar activity as reference, and
per were requested only when in doubt about the final conclusion was reached by consen-
the diagnosis. Brain CT scans were obtained sus. Deviations of tracer concentration from
for all patients. Patients suspected to have normal were graded as mild, moderate and
cardiac disturbances were submitted to an marked.
echocardiogram. All patients were seen by a Data were analyzed statistically by the
cardiologist regardless of symptoms. Mann-Whitney test to compare disease du-
All patients were treated with haloperi- ration between patients with a normal or
dol or pimozide, both at initial doses of 1 mg abnormal SPECT examination, with the level
which were gradually increased until symp- of significance set at 5%.
toms were reduced or produced adverse ef-
fects. All patients received prophylactic treat- Results
ment with benzathine penicillin, 1,200,000
IU every 15 days. We investigated 10 patients, 8 females
Follow-up consisted of consultations and 2 males. Table 1 shows the clinical and
at 3-month intervals over a period of 6 to brain SPECT findings of the patients. None
24 months and none of the patients had of the patients had a previous streptococcal
recurrence or chronic manifestation of cho- infection but 5 of them reported a complaint
rea. of a recent sore throat (patients Nos. 2, 3, 4,
All patients were submitted to brain 9 and 10). Association of arthritis and chorea
SPECT imaging at the Nuclear Medicine was seen in patients Nos. 1, 4 and 9. Two
Unit of the Federal University of São Paulo. patients (Nos. 3 and 10) had clinical evi-
HMPAO (Ceretec, Amersham Pharmacia dence of carditis. No evidence of abnormal
Biotech, Uppsala, Sweden) labeled with tech- neuropsychiatric features such as obsessive-
netium-99m (99mTC-HMPAO) was used as compulsive symptoms or mood changes was
the radiotracer (11). All patients had an in- observed in any of the patients. Age ranged
travenous access line placed in the arm and from 8 to 25 years (mean ± SD: 13.4 ± 4.8
remained at rest, with their eyes open, for 30 years). Mean time interval from onset of
min in a quiet room with dim light. A dose of abnormal movements to consultation was
740 MBq (20 mCi) of the radiotracer was 63.6 days, with a standard deviation of 59.7.
injected and image acquisition was started All patients presented abnormal movements
15 min later. A single-head scintillation cam- ranging from mild and only distal choreic
era (Apex SPX-4, Elscint, Haifa, Israel) movements (such as patient 6) to severe
equipped with a low-energy parallel hole generalized chorea with hypotonia (such as
collimator was used. The photopeak was patient 9). All patients had normal brain CT
centered at 140 keV with a 20% symmetric scans.
window. Images were acquired with a 64 x The cerebral SPECT was abnormal in 6
64 matrix without zoom for 360 degrees in a patients, revealing hyperperfusion of the basal
continuous circular orbit. A total of 60 im- ganglia. All patients with abnormal brain
ages were taken at 6-degree intervals for 20 SPECT were females. Patients with abnor-
s each and a total acquisition time of 20 min. mal brain SPECT had experienced symp-
After attenuation correction, images were toms for 49 days on average, as compared to
reconstructed on the transaxial, coronal and 85 days for patients with normal SPECT.
sagittal planes and displayed for interpreta- This difference was not statistically signifi-
tion. Three nuclear medicine experts, with cant. Figure 1 shows the brain SPECT find-
no knowledge of the clinical status of the ings of 2 patients. All patients were on halo-
patients, interpreted the images visually us- peridol or pimozide at the time of the study.
Braz J Med Biol Res 35(4) 2002
434 O.G.P. Barsottini et al.
Discussion possibly due to changes in the basal ganglion
microcirculation or to a blood-brain barrier
All patients with abnormal unilateral or abnormality secondary to the infectious pro-
bilateral brain SPECT showed hyperconcen- cess (12). Vasculitis in basal ganglia is ob-
tration of the radiotracer in the basal ganglia, served in SC patients submitted to histologi-
Table 1. Clinical characteristics of Sydenham’s chorea patients submitted to brain single-photon emission
computed tomography (SPECT).
Patient # Gender Age Duration from Clinical findings SPECT
(years) onset to
1 F 12 60 Mild choreic movements R>L, dysarthria Abnormal*
2 F 14 150 Mild bilateral choreic movements Abnormal
3 M 9 60 Mild bilateral choreic movements Normal
4 F 14 30 Moderate bilateral choreic movements Abnormal
5 F 12 180 Mild bilateral choreic movements Normal
6 M 17 90 Mild unilateral chorea (L) Normal
7 F 25 20 Mild choreic movements L>R, dysarthria Abnormal
8 F 13 6 Moderate bilateral choreic movements, Abnormal
dysarthria and hypotonia
9 F 8 10 Severe bilateral choreic movements, Normal
10 F 10 30 Mild bilateral choreic movements Abnormal
*All patients with abnormal SPECT had a hyperconcentration of radiotracer in basal ganglia. L, left; R, right.
Figure 1. Brain single-photon Patient 2: abnormal SPECT
emission computed tomography
(SPECT) imaging of patient 2 (ab-
normal) and patient 3 (normal).
The arrowheads in abnormal
SPECT (patient 2) indicate the
basal ganglia in which an abnor-
mal study presents a hypercon-
centration of tracer.
Patient 3: normal SPECT
Braz J Med Biol Res 35(4) 2002
Brain SPECT in Sydenham’s chorea 435
cal postmortem examination (13). The in- patients but none of them had evidence of
creased radiotracer uptake by basal ganglia any other disease.
could be explained by a blood-brain barrier All patients with abnormal brain SPECT
abnormality induced by the inflammatory (6 patients) were females. Although the re-
process. duced number of patients studied does not
In the present study we detected abnor- permit us to conclude that this could apply to
mality of the basal ganglia in 6 of 10 patients. all SC patients, female patients seem to have
This is an expressive number of patients but a peculiar clinical evolution of SC as com-
we cannot explain why 4 patients had a pared to male patients, probably due to hor-
normal brain SPECT despite the presence of monal factors (16). We could speculate that
SC. Interestingly, we observed that the most these hormonal factors may lead to more
symptomatic patients were not necessarily prominent inflammatory activity in the basal
those with an abnormal brain SPECT study. ganglia and to an abnormal brain SPECT
Patient 9, for instance, had severe chorea but study.
her brain SPECT was normal. Perhaps the Our group of patients with abnormal brain
inflammatory process in the basal ganglia is SPECT averaged 49 days of disease, as op-
not directly correlated with the severity of posed to 85 days for patients with normal
the clinical manifestations. Another expla- studies. This difference did not reach statis-
nation for the normal SPECT studies is that tical significance but perhaps a larger num-
the image analysis of the SPECT is based on ber of patients could confirm this finding.
subjective visual criteria, even though our This inverse relationship between duration
Nuclear Medicine staff is experienced in the of the disease and abnormal brain SPECT
interpretation of these studies. In addition, does not explain patient 2 who had an abnor-
three experts had to reach a consensus for mal test 150 days after the onset of symp-
the final result. An additional explanation is toms. We may speculate that disease dura-
our incomplete understanding of the patho- tion could be one of the factors involved in
physiology of SC. For instance, we do not the abnormality. Other factors, such as re-
know whether the vasculitis is directly re- current streptococcal infection, might also
lated to the presence of the choreic move- be involved.
ments or if it is simply an epiphenomenon We also know that the brain SPECT ab-
(14). Therefore, the patients with normal normality in SC can be reversed (17-19).
brain SPECT examinations would just re- The normal examination observed in some
flect those with chorea but without vasculi- of our patients could reflect the phase of
tis. brain SPECT normalization.
All of our 10 patients had clinical ab- Unfortunately, we did not repeat the brain
normalities consistent with the diagnosis of SPECT on any of our patients. Normaliza-
SC, including insidious onset, choreic move- tion of the study after disappearance of symp-
ments, presence of restlessness, psychologi- toms would be a demonstration of the speci-
cal and emotional disturbances and muscu- ficity and sensitivity of brain SPECT imag-
lar hypotonia (15). We could not establish ing for choreic patients.
the correlation between the beta-hemolytic In conclusion, we believe that brain
streptococcus and the onset of abnormal SPECT can be a helpful method to identify
movements since in all situations the ASLO different phases of SC. A larger number of
examination was within normal limits. An patients could help to identify the phase of
alternative diagnosis such as antiphospho- the disease during which brain SPECT imag-
lipid syndrome could be proposed for some ing is most useful.
Braz J Med Biol Res 35(4) 2002
436 O.G.P. Barsottini et al.
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