Chorea and antiphospholipid antibodies: Treatment with methotrexate

Abstract

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][4][5] We report the correlation between clinical symptoms, laboratory activity of aPL, and striatal hypermetabolism in 18 F-fluorodeoxyglucose (FDG) PET in a patient with aPL-associated hemichorea. This patient was successfully treated with low-dose methotrexate.Case report. 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, intraand 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, Ͻ1.2); the anticardiolipin antibody titer (IgG) (aCL-IgG) was elevated (86.0 U/mL; normal, Ͻ18 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 aCLIgG (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 Ϯ 1.5%; p Ͻ 0.05) (figure).Medication was started again at 20 mg methotrexate per week. After 2 weeks, choreatic movements were no longer detectable. After 6 weeks of co...

Hemichorea with antiphospholipid antibodies in a patient with lupus nephritis

“…However, because aPLs were produced by immunemediated mechanisms, immunosuppressive treatments such as high-dose corticosteroids, cyclophosphamide, and combinations of the two, or methotrexate have been employed in most patients with aPLs-associated chorea [12]. Since our patient had already been treated with cyclophosphamide, we used mizoribine as an immunosuppressive drug, which reduced our patient's aPLs titers and resulted in the chorea subsiding.…”

Testing for Antiphospholipid Antibody (aPL) Specificities in Retrospective “Normal” Cerebral Spinal Fluid (CSF)

“…These include focal central nervous system thrombo-occlusive events (Levine et al, 2002), chorea (Paus et al, 2001), migraine headaches (Silvestrini et al, 1993), amnesia (Montalban et al, 1989), visual abnormalities (Briley et al, 1989), as well an psychosis (Chengappa et al, 1991;Schwartz et al, 1998) and cognitive dysfunction (Denberg et al, 1997;Jacobson et al, 1999). The associations of aPL with neurologic conditions other than thromboocclusive events have been considered "weak" and attributable to an "epiphenomenon" rather than to pathophysiologic mechanisms (Brey, 2000).…”

Hemichorea with antiphospholipid antibodies in a patient with systemic lupus erythematosus

“…Because aPLs were produced by immune mediated mechanisms, immunosuppressive treatments such as high dose corticosteroids, cyclophosphamide, combinations of the two, or methotrexate have been employed in most patients with aPL associated chorea 2 , 14. Therapy with combined intravenous methylprednisolone and monthly cyclophosphamide appears to have been effective in our patient.…”