Nimet Kabakus, *Tansel Ansal Balci, Abdullah Kurt and Aysegul Nese Citak Kurt

From the Department of Pediatrics, Firat University, Faculty of Medicine, and *Department of Nuclear Medicine, Firat University, Faculty of Medicine, Elazig, Turkey.

Corresponding to: Dr. Nimet Kabakus, Firat University, Faculty of Medicine, Department of Pediatric Neurology, 23119, Elazig / Turkey. E-mail:[email protected]

Manuscript received: December 7, 2004, Initial review completed: February 15, 2005;
Revision accepted: December 3, 2005.

 

Abstract:

Functional imaging studies in patients with Sydenham’s chorea have suggested brain perfusional abnormalities. In this study, we aimed to investigate the cerebral perfusion patterns of the cortical/subcortical structures by using Tc-99m hexamethylpropylenamine oxime single photon emission computed tomography in children with Sydenham’s chorea, accompanied with magnetic resonance imaging and cranial Doppler studies. Brain MRI and Doppler studies of the all cases were normal. In the brain SPECT study, six patients were determined to have cerebral perfusion abnormalities. Although six patients responded well to the therapy, two girls who had hypoperfusion in the right frontal region as well as hypo- / hyperperfusion in the basal ganglia did not respond to therapy. While the chorea form of the patients who have cerebral perfusional abnormality was generalized, the clinical picture of the patients with normal cerebral perfusion was in the form of hemichorea.

Key words: Brain SPECT, Sydenham’s chorea, Tc-99m HMPAO.

Sydenham’s chorea (SC) is one of the major diagnostic criteria of acute rheumatic fever (ARF), 80% of SC patients are children and adolescents in age group between 5-15 years and especially girls. Immunologic, genetic and personal characteristics are known to be responsible. These patients are supposed to have antibodies against subthalamic and caudate nucleus(1-3).

Vascular lesions in the basal ganglia and the substantia nigra and variations in the blood-brain barrier in the patients with SC are known(1,4). Furthermore, perfusion abnormalities in the basal ganglia of some patients with SC have been reported in the single photon emission computed tomography (SPECT) studies. These perfusion abnormalities sometimes may have prognostic value. Whereas hyperperfusion is a good prognostic symptom, hypoperfusion can be a bad one(3-7).

Brain scintigraphy using technetium-99m hexamethylpropyleneamine oxime (Tc-99m HMPAO) SPECT technique allows blood perfusion assessment of the brain. Tc-99m HMPAO is the first neutral-charged lipophilic Tc-99m chelate with rapid uptake and prolonged cortical retention. After intra-venous injection, it can normally cross the intact blood-brain barrier and diffusely distribute throughout the cerebral cortex proportional to regional blood flow (rCBF). It has a great acceptance for routine neuro-SPECT imaging. Consequently, subsequent images indicate the defined neuro-physiological state present at the time of injection(6,7). HMPAO brain SPECT has the ability to detect abnormal rCBF in patients who may have normal appearing in the CT and MRI scans(5-7). The studies performed by SPECT for basal ganglia disorders indicate that SPECT is a useful method to evaluate basal ganglia functions including neuro-degenerative disorders(1,3-6).

With this background, we investigated brain perfusion abnormalities by using brain SPECT accompanied with brain MRI and cranial Doppler in patients with SC.

Of the 14 patients who had acute rheumatic fever with chorea, eight patients (5 girls, 3 boys, aged between 7-15 years) whose SPECT study could be carried out were included in the study. Inclusion criteria were: presence of choreic movements with onset within the last six months, and age from 5 to 15 years. Informed consent was obtained from the parents and children before being enrolled. SC was diagnosed according to modified Jones criteria(1-3). Following tests and laboratory studies were carried out: whole blood count including white blood cell count (WBC), erythrocyte sedimentation rate (ESR), hepatic and renal function tests, anti- streptolysin O (ASO), C-reactive protein (CRP), serum and urine copper level, serum ceruloplasmine, urine/blood amino acid, X-ray chest, electro-cardiography and echocardiography. All laboratory and imaging (Doppler, MRI and SPECT) were completed within 24 hours of admission.

The cranial arterial Doppler was done using Toshiba Aplio. MRI studies were performed on a 0.3-T open Hitacy scanner. A 3-mm slice thickness was used. During cranial analysis, the following sequences were applied: Spin Echo T1, Proton Density and Fast Spin Echo T2. To evaluate the basal ganglia, 3D coronal spoiled gradient echo sequence was added. After obtaining sequences, the brain structures of the patients were evaluated visually.

In the scintigraphic study, half an hour before the radiopharmaceutical injection, an intravenous cannula was inserted to an appropriate peripheral vein of the patient. Then the patient relaxed under optimal conditions for the brain scintigraphy. An average 0.3 mCi/kg dose of Tc-99m HMPAO (Brain-SPECT, Medi-Radiopharma Ltd, Budapest, Hungary) was injected intra-venously to the patient in a quiet, dimmed room. Sedation of the patient, if necessary, was ensured with chloral hydrate (50-75 mg/kg/dose) and/or midazolam (0.05 mg/kg/dose) at least half an hour after the injection. Image acquisition started approximately at one hour postinjection. A single-head gamma camera (Toshiba GCA 602A) equipped with the general purpose, low-energy, parallel-hole collimator was used in the scintigraphic study. The patient was positioned supine on the imaging table under the gamma camera. Patient’s head was fixed with a Velcro restraint and made motionless. Gamma camera acquisition parameters were used as following: totally 60 images each of which was 25 seconds duration, at 64 × 64 matrices, per 360 degree rotation. Then the data were reconstructed according to the predetermined protocol on the camera software. Images were applied × 2 magnification for a better visual evaluation. Two nuclear medicine specialists regarding hypo and hyperperfusion evaluated the obtained images at transaxial, coronal and sagittal tomographic slices visually.

SC patients were treated with medical therapy (penicillin prophylaxis and halo-peridol at a dose of 3 mg/day, b.i.d.). Two girl patients (cases no 2 and 6) who did not respond to both the haloperidol and the valproic acid therapy, underwent corticosteroid therapy(8).

Summary of the clinical and laboratory features of SC patients are shown in Table I. Mean age of the patients was 10.8 ± 3.1 years (7-15 years). The majority of the patients (n = 5, 62.5%) consisted of the girls and streptococcal history existed only in half of the cases. The medium duration from onset to evaluation was 5.1 ± 2.8 (2-10) weeks.

Brain MRI and cranial arterial Doppler study of all patients were normal.

Although six patients responded well to the therapy, two girl patients (no 2 and 6) did not respond to both the haloperidol and valproic acid therapy, and thereafter these patients underwent corticosteroid therapy(8). Corticosteroid protocol consisted of two phases. Phase 1 involves pulse-therapy with intravenous methyl-prednisolone, 25 mg/kg/day, for 5 consecutive days. For phase 2, after the completion of the pulse-therapy, the patients were discharged on oral prednisone (1 mg/kg/day) started on day 6. The oral form was gradually tapered down. Although the chorea findings of these patients decreased, they are still continuing.

In the brain SPECT study, six patients were detected to have abnormal rCBF (Table I): (i) Three patients had isolated left basal ganglia hypoperfusion, (ii) Three patients had hypoperfusion in the right (n = 2) and left (n = 1) frontal regions as well as hypoperfusion (n = 2) or hyperperfusion (n = 1) in the basal ganglia, (iii) Two patients had normal cerebral perfusion. There was no relationship between the severity of the hypoperfused areas and arthritis/carditis. Three patients had arthritis and chorea, and there was a strange co-existence between these major criteria. While the chorea form of the patients who had cerebral perfusional abnormality was generalized, the clinical picture of the patients with normal cerebral perfusion was in the form of hemichorea. The chorea findings of the patients who had perfusion abnormalities in the basal ganglia and the right frontal area were severe and these patients did not respond well to the therapy.

SC is the most common acquired chorea of childhood and is the sole neurological manifestation of RF. SC occurs in 10-20% of patients with RF. Cardiac involvement in SC has been reported in 23-84%, whereas association with arthritis does not exceed 30% (3-5).

It has been known that in some infectious/inflammatory situations, the basal ganglia microcirculation and/or blood-brain barrier demonstrate changes (3,4,10). The primary pathologic finding is vasculitis of the cortical arterioles with round cell infiltration of the gray and white matter in the surrounding area, possibly the results of the cellular response to antineuronal antibodies. In the histological studies, it has been proved that in the patients with SC, vasculitis develops in the basal ganglia and this causes destruction in the blood-brain barrier. The perfusional changes visualized in brain scintigraphy are the result of this destruction(1,4).

There are few reports about the brain SPECT in SC (1, 3,). Lee, et al. (10) reported a case, showing hyperperfusion of the basal ganglia and Dilenge, et al.(11) reported two cases, showing hyperperfusion. Alternately, Hill, et al.(5) reported a case showing no abnormality and Heye, et al.(4) reported a case showing hypoperfusion in striatum.

It has been known that there is a relationship between the basal ganglia perfusional changes in the brain SPECT studies and clinicopathological situation (3-7). There are studies proving that hypoperfusion in basal ganglia develops in degenerative cases, whereas hyperperfusion develops in the infectious/inflammatory situations (1,3-7).

There is streptococcal infection anamnesis in half of our patients. The duration time of the symptoms of SC is less than 1 month in 4 patients (50%). This period is less than the time interval reported in the literature(1-4). Because all of our patients were students, their teachers could notice abnormal movements earlier and/or the racial and geographical differences could be the reason of the short duration. Presentation of the brain SPECT as normal in two patients showing short latent period with active ARF can be interpreted being necessary a definite time for the visualization of the abnormal perfusion pattern in SPECT imaging.

We could not find any relation between the clinical picture and the isolated SC or SC accompanied with the major findings, and the rCBF findings. For example, clinical manifestations, response to therapy and SPECT findings of the patient 2 who had chorea alone and the patient 6 who had chorea with carditis were similar. We could not determine a significant difference about the SPECT findings between the girls and boys.

In our study, cranial Doppler study was found normal in the patients. We suppose that there was no gross cerebral blood-flow abnormality in the patients with SC. However, it will not be an honest attitude to interpret our MRI findings as exactly normal because of the low tesla (0.3 T) of existing MRI device. Such abnormalities were reported with more advanced MRI device(12). To design a study consisting more patients with more sensitive combined techniques (such as PET, diffusion-weighted imaging and proton MR spectroscopy, excitatory/inhibitory neurotransmitters and performance tests) may be more clarifying for all these possible relationships.

Contributors: NK prepared the protocol, drafted the manuscript, conceptualised and designed the study and management of patient; TAB involved in carrying out SPECT studies; AK supervised and monitored Laboratory work and ANC participated in collection and interpretation of data.

Funding: None.

Competing interests: None.
 

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