Chorea and antiphospholipid antibodies: Treatment with methotrexate
S. Paus, MD;,
B. Pötzsch, MD;,
J. H. Risse, MD;,
T. Klockgether, MD and
U. Wüllner, MD
From the Departments of Neurology (Drs. Paus, Klockgether, and Wüllner) and Nuclear Medicine (Dr. Risse), and the Institute of Experimental Haematology and Transfusion Medicine (Dr. Pötzsch), University of Bonn, Germany.
Address correspondence and reprint requests to Dr. S. Paus, Neurologische Universitätsklinik, Neurobiologisches Labor, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany; e-mail spaus{at}uni-bonn.de
Chorea may occur in systemic lupus erythematosus (SLE) and primaryantiphospholipid antibody syndrome (PAPS). Vascular lesionsand immune-mediated excitatory mechanisms have been proposedas the underlying pathophysiology.1,2 Accordingly, immunosuppressivetherapy has been employed in antiphospholipid antibody (aPL)-associatedchorea.3-5 We report the correlation between clinical symptoms,laboratory activity of aPL, and striatal hypermetabolism in18F-fluorodeoxyglucose (FDG) PET in a patient with aPL-associatedhemichorea. This patient was successfully treated with low-dosemethotrexate.
A 41-year-old right-handed woman developed involuntary movementsof the left hand in June 1999. Within 2 weeks, the symptomsprogressed to uncontrollable jerks of the left arm and leg,with clumsiness of finger movements, twitching of the left facewith squeezing of the eye, and speech difficulties due to clumsinessof the tongue. She was unable to continue working. Her medicalhistory included moderate hypertension treated with losartan50 mg per day, hysterectomy, and cigarette smoking (12 pack-years).Family history of movement disorders was negative.
A cranial MRI revealed no ischemic lesion. CSF, EEG, intra-and extracranial DCI, and ophthalmologic examination resultswere normal. Tests for lupus anticoagulant (LA) were positive,with increased activated partial thromboplastin time (aPTT)(38.7 s; normal, 21.0 to 36.0 s) and dilute Russell viper venomtime ratio (dRVVT-ratio) (2.2; normal, <1.2); the anticardiolipinantibody titer (IgG) (aCL-IgG) was elevated (86.0 U/mL; normal,<18 U/mL). All other laboratory results including plateletcount, complement factor 3 and 4, anti–ds-DNA antibodies,antinuclear antibodies, HIV antibodies, treponema pallidum hemagglutinationassay (serum and CSF), acanthocytes, serum copper and ceruloplasmin,and thyroid function were normal. A preliminary diagnosis ofaPL-associated chorea was made.
Six weeks after the first manifestation of chorea, treatmentwas initiated with low-dose methotrexate, 20 mg orally onceper week, which led to a rapid improvement. After 4 weeks ofcontinuous medication, choreatic movements were no longer detectableand the laboratory follow-up showed an improved result for aCL-IgG(55.7 U/mL) and a downward trend of LA (aPTT 34.5 s; dRVVT-ratio1.7).
Methotrexate treatment was discontinued after 9 weeks. Eightdays after the last intake, the patient again noticed involuntary movements of the left hand and foot. Neurologic examination12 days after the last methotrexate intake confirmed a mildto moderate relapse of left-sided hemichorea. Laboratory resultsshowed increased LA (aPTT 39.5 s; dRVVT-ratio 1.9) and aCL-IgG(75.2 U/mL). An FDG PET performed to study striatal hypermetabolismrevealed an increase of FDG uptake in the right caudate nucleusas compared with the left side (6.36 ± 1.5%; p < 0.05)( figure).
Figure. 18F-fluorodeoxyglucose (FDG) PET during a relapse after withdrawal of methotrexate. FDG uptake is enhanced in the right caput nuclei caudati (CNC) as compared with the contralateral side. Regions of interest in this plane revealed maximal standard uptake values of 6.3 (right CNC) and 5.8 (left CNC).
Medication was started again at 20 mg methotrexate per week.After 2 weeks, choreatic movements were no longer detectable.After 6 weeks of continuous medication, FDG PET revealed nodifference between FDG uptake values of the left and right caudatenucleus. The laboratory follow-up showed a downward trend ofdRVVT-ratio (1.7) and aCL-IgG (67.3 U/mL), whereas aPPT wasnearly unchanged (42.0 s).
This case of aPL-associated hemichorea documents an associationbetween intensity of choreatic symptoms, laboratory activityof aPL, striatal hypermetabolism, and immunosuppressive therapywith methotrexate. Our results are consistent with earlier suggestionsthat aPL-associated chorea is caused by an immune-mediated excitatoryeffect of aPL resulting in striatal hypermetabolism measurableby PET, rather than a consequence of ischemic lesions in thebasal ganglia.5,6
Chorea associated with aPL in adults has been reported in SLE,lupus-like syndrome, and PAPS.3 In patients who do not fulfillthe criteria of the American College of Rheumatologists forthese disorders, as in our case, chorea might be an early symptomof SLE or PAPS, antedating the disease for several years,3 orthe only manifestation of aPL.
A search of the literature revealed high-dose corticosteroids,cyclophosphamide, and combinations of the two as the most frequentlyused medication in aPL-associated chorea. The dramatic responseto oral application of low-dose methotrexate, however, demonstratesthat treatment with methotrexate alone may provide a reasonableand effective alternative.
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Received June 1, 2000.
Accepted in final form August 24, 2000.
This article has been cited by other articles:
A. V. Brochado, S. Pimenta, M. Silva, R. Sousa, M. M. Campos, and I. Brito Hemichorea with antiphospholipid antibodies in a patient with systemic lupus erythematosus
BMJ Case Reports,
August 18, 2009;
2009(aug18_1):
bcr1220081339 - bcr1220081339.
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