Neurology 2001;56:137-138
© 2001 American Academy of Neurology
Clinical/Scientific Notes
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
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Introduction
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Chorea may occur in systemic lupus erythematosus (SLE) and primary antiphospholipid antibody syndrome (PAPS). Vascular lesions and immune-mediated excitatory mechanisms have been proposed as the underlying pathophysiology.1,2 Accordingly, immunosuppressive therapy has been employed in antiphospholipid antibody (aPL)-associated chorea.3-5 We report the correlation between clinical symptoms, laboratory activity of aPL, and striatal hypermetabolism in 18F-fluorodeoxyglucose (FDG) PET in a patient with aPL-associated hemichorea. This patient was successfully treated with low-dose methotrexate.
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Case report.
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A 41-year-old right-handed woman developed involuntary movements of the left hand in June 1999. Within 2 weeks, the symptoms progressed to uncontrollable jerks of the left arm and leg, with clumsiness of finger movements, twitching of the left face with squeezing of the eye, and speech difficulties due to clumsiness of the tongue. She was unable to continue working. Her medical history included moderate hypertension treated with losartan 50 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 results were 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 venom time ratio (dRVVT-ratio) (2.2; normal, <1.2); the anticardiolipin antibody titer (IgG) (aCL-IgG) was elevated (86.0 U/mL; normal, <18 U/mL). All other laboratory results including platelet count, complement factor 3 and 4, anti–ds-DNA antibodies, antinuclear antibodies, HIV antibodies, treponema pallidum hemagglutination assay (serum and CSF), acanthocytes, serum copper and ceruloplasmin, and thyroid function were normal. A preliminary diagnosis of aPL-associated chorea was made.
Six weeks after the first manifestation of chorea, treatment was initiated with low-dose methotrexate, 20 mg orally once per week, which led to a rapid improvement. After 4 weeks of continuous medication, choreatic movements were no longer detectable and 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-ratio 1.7).
Methotrexate treatment was discontinued after 9 weeks. Eight days after the last intake, the patient again noticed involuntary movements of the left hand and foot. Neurologic examination 12 days after the last methotrexate intake confirmed a mild to moderate relapse of left-sided hemichorea. Laboratory results showed increased LA (aPTT 39.5 s; dRVVT-ratio 1.9) and aCL-IgG (75.2 U/mL). An FDG PET performed to study striatal hypermetabolism revealed an increase of FDG uptake in the right caudate nucleus as compared with the left side (6.36 ± 1.5%; p < 0.05) ( figure).
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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).
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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 no difference between FDG uptake values of the left and right caudate nucleus. The laboratory follow-up showed a downward trend of dRVVT-ratio (1.7) and aCL-IgG (67.3 U/mL), whereas aPPT was nearly unchanged (42.0 s).
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Discussion.
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This case of aPL-associated hemichorea documents an association between intensity of choreatic symptoms, laboratory activity of aPL, striatal hypermetabolism, and immunosuppressive therapy with methotrexate. Our results are consistent with earlier suggestions that aPL-associated chorea is caused by an immune-mediated excitatory effect of aPL resulting in striatal hypermetabolism measurable by PET, rather than a consequence of ischemic lesions in the basal 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 fulfill the criteria of the American College of Rheumatologists for these disorders, as in our case, chorea might be an early symptom of SLE or PAPS, antedating the disease for several years,3 or the only manifestation of aPL.
A search of the literature revealed high-dose corticosteroids, cyclophosphamide, and combinations of the two as the most frequently used medication in aPL-associated chorea. The dramatic response to oral application of low-dose methotrexate, however, demonstrates that treatment with methotrexate alone may provide a reasonable and effective alternative.
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References
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Cervera R, Asherson RA, Font J, et al. Chorea in the antiphospholipid syndrome. Medicine (Baltimore) 1997; 76: 203–212.[Medline]
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Van Horn G, Arnett FC, Dimachkie MM. Reversible dementia and chorea in a young woman with the lupus anticoagulant. Neurology 1996; 46: 1599–1603.[Abstract/Free Full Text]
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Sunden–Cullberg J, Tedroff J, Aquilonius S-M. Reversible chorea in primary antiphospholipid syndrome. Mov Disord 1998; 1: 147–149.
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Furie R, Ishikawa T, Dhawan V, Eidelberg D. Alternating hemichorea in primary antiphospholipid syndrome: evidence for contralateral striatal hypermetabolism. Neurology 1994; 44: 2197–2199.[Abstract/Free Full Text]
Received June 1, 2000.
Accepted in final form August 24, 2000.
Top.
Introduction
Case report.
