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Parkinsonism as a manifestation of neuropsychiatric systemic lupus erythematosus: a case report and literature review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a subtype of SLE specifically involved in neurologic manifestations usually observed in central, peripheral, and autonomic nervous systems and sometimes with psychiatric disorders. (1) Movement disorders such as chorea, ataxia, and hemiballismus have been described in the American College of Rheumatology classification of NPSLE. (2) However, parkinsonism, as a movement disorder, is an extremely rare manifestation of NPSLE. Here, we report a patient of NPSLE with parkinsonism.


A 17-year-old girl was admitted to our hospital after one month of fever, hand erythema, and arthralgia. There were no significant findings in her personal or family history. Results from blood test showed leucopenia (white blood cell 2.7 * [10.sup.9]/L); positive antinuclear antibody (1:1000), anti-double stranded (ds) DNA, anti-Sjogren syndrome A antigen, anti-Sjogren syndrome B antigen, and anti-ribosome P protein; negative antiphospholipid antibody, anti-beta2GP1 antibody, and anti-neutrophil cytoplasmic antibodies (low complement 3 (0.31 g/L) and high erythrocyte sedimentation rate (89 mm/h). Urine test showed no hematuria or proteinuria. According to the 1982 revised criteria for the classification of SLE, she was diagnosed with SLE. The Systemic Lupus Erythematosus Disease Activity Index score was 16. She was administered with intravenous methylprednisolone (80 mg/day, her weight was 50 kg) for three consecutive days, followed by intravenous methylprednisolone (40 mg/day) and oral hydroxychloroquine (200 mg/day). Six days later, her temperature returned to normal, erythema almost disappeared, and arthralgia was significantly relieved. However, during this one-week period, she developed a progressive slowdown of motor response, movement, thinking, speech, and reaction to stimuli. She did not complain of any limb weakness or numbness, giddiness, diplopia, tinnitus, urinary or bowel dysfunction. Neurological examinations showed that she was fully oriented with no evidence of cognitive dysfunction, aphasia, paresthesia, meningism, lateralizing neurological deficits, or cranial nerve palsies. With disease progression, she developed obvious expressionless face, bradykinesia, marked rigidity, and hypermyotonia in her extremities. She also had a festinating gait with only slight arm swing, and her gaits turned and started in hesitation but without rest or action tremor.

Head magnetic resonance imaging showed symmetrical long T1 signal, slight long [T.sub.2] signal, and high [T.sub.2] flair signal in bilateral basal ganglia, hippocampus, insular lobe, and subcortex of frontal gyrus rectus. Bilateral external capsule showed long T1 signal, long [T.sub.2] signal, and high [T.sub.2] flair signal (Figure 1). Enhanced magnetic resonance imaging showed a slightly increased signal intensity of bilateral basal ganglia. Lumbar puncture showed that the cerebrospinal fluid (CSF) was colorless and transparent with CSF pressure at 120 mm[H.sub.2]O. Biochemical test of CSF showed normal levels of protein (175 mg/L), glucose (3.1 mmol/L), lactate dehydrogenase, chloride, and adenosine deaminase, but a slight elevation of white blood cells (25 * [10.sup.6]/L). CSF smear, culture, Gram staining, acid-fast staining, tuberculosis DNA, virus antibody test, and fungal test were all negative. Autoantibodies to dsDNA and ribosomal P protein were positive in the CSF, but anti-phospholipid, anti-beta2GP1, anti-neuronal, anti-glial fibrillary acidic protein, anti-endothelial cell, and anti-N-methyl-D-aspartate antibodies were negative. Since none of the drugs administered appeared to have potential side effect of parkinsonism and no other causes of parkinsonism could be recognized for this particular patient, she was considered to have NPSLE.

High dose intravenous methylprednisolone (500 mg/day) was prescribed for three days followed by oral prednisolone (1 mg/kg/day), and intravenous cyclophosphamide (600 mg/[m.sup.2] body surface area) was prescribed once. Intrathecal injection of methotrexate (MTX) (10 mg) and dexamethasone (DXM) (10 mg) were applied once a week for two weeks. After these treatments, the patient showed steady improvements in her gait, speech and movements. Two weeks later, her blood showed normal level of complement 3 (0.84 g/L) and erythrocyte sedimentation rate (18 mm/h). She was discharged on maintenance of oral prednisolone (30 mg/day), oral hydroxychloroquine (200 mg/day), and intravenous cyclophosphamide (800 mg/month). At the patient's two-month follow-up visit, we noticed that she had normal facial expression, speech, movement, and gait. Complement 3 (0.86 g/L) and erythrocyte sedimentation rate (12 mm/h) remained normal and the titer of antinuclear antibody decreased to 1:40. The Systemic Lupus Erythematosus Disease Activity Index was reevaluated with a score of 0. Patient was still in remission at nine-month follow-up, and her head magnetic resonance imaging was normal (Figure 1).


Neuropsychiatric systemic lupus erythematosus associated parkinsonism was first described by Seminario and Pesano in 1930. (3) Since then, only about 30 NPSLE cases with parkinsonism have been reported to date (Table 1). (3-19) Autoantibodies and immune-mediated vasculopathy was suggested in the pathogenesis of parkinsonism in NPSLE. (20) Kunas et al. (4) found antibodies to dopaminergic cells in serum from the NPSLE patients manifested with parkinsonism. They concluded that antidopamine antibodies could be specific to NPSLE patients with parkinsonism. However, to our knowledge, there are no controlled trials of any treatment for NPSLE with parkinsonism. Improvements have been reported in those patients treated with combination of steroids and cyclophosphamide, with or without anti-parkinsonian drugs. (10) In two cases, intravenous injection of immunoglobulins appeared to be effective after methylprednisolone and cyclophosphamide failed. (11) Intrathecal injection of MTX plus DXM, which was assumed to enhance the immunosuppressive effects but reduce side effects, has been shown to improve the outcomes of NPSLE patients without parkinsonism. (21) To our knowledge, our patient was the first NPSLE patient with parkinsonism reported to accept intrathecal injection of MTX plus DXM and obtain a satisfactory outcome. Although there was no control in our therapeutic regimen, results from this particular case support the notion that intrathecal injection of MTX and DXM, plus high dose intravenous methylprednisolone and cyclophosphamide for NPSLE patients with parkinsonism may be a plausible therapeutic strategy.

doi: 10.5606/ArchRheumatol.2015.5456

Declaration of conflicting interests

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.


The authors received no financial support for the research and/or authorship of this article.


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(14.) Osawa H, Yamabe H, Kaizuka M, Tamura N, Tsunoda S, Shirato KI, et al. Systemic lupus erythematosus associated with transverse myelitis and parkinsonian symptoms. Lupus 1997; 6:613-5.

(15.) Lim SM, Oldfield M, Abbott RJ. Systemic lupus erythematosus presenting with steroid-responsive parkinsonism and post-hemiplegic dystonia. Eur J Neurol 1998; 5:309-312.

(16.) Chacon J, Garcia-Moreno JM, Valencia J, Redondo L, Alegre S, Castro A, et al. Parkinson disease of juvenile onset with systemic lupus erythematosus in a pre-symptomatic stage. Rev Neurol 1999; 29:725-7. [Abstract]

(17.) Tan EK, Chan LL, Auchus AP. Reversible parkinsonism in systemic lupus erythematosus. J Neurol Sci 2001; 193:53-7.

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(21.) Valesini G, Priori R, Francia A, Balestrieri G, Tincani A, Airo P, et al. Central nervous system involvement in systemic lupus erythematosus: a new therapeutic approach with intrathecal dexamethasone and methotrexate. Springer Semin Immunopathol 1994; 16:313-21.

Qi TANG, [1] Jing WANG, [2] Jinwei CHEN, [1] Xi XIE, [1] Jing TIAN [1]

[1] Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, China

[2] Department of Rheumatology and Immunology, First People's Hospital Of Yunnan Province, Yunnan, China

Received: October 05, 2014 Accepted: March 14, 2015 Published online: June 13, 2015

Correspondence: Jing Tian, MD. Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, 410011 Changsha, China. Tel: +86 136 37 31 21 58 e-mail:

Table 1. Summary of cases of reported neuropsychiatric systemic
lupus erythematosus patients with parkinsonism

Author                          Age/gender   EEG   MRI   SPECT

Seminario and Pessano (3)          17/M       N     N      N
Seminario and Pessano (3)          19/F       N     N      N
Seminario and Pessano (3)          30/F       N     N      N
Seminario and Pessano (3)          23/F       N     N      N
Kunas et al. (4)                   34/F       N     -      +
Poch (5)                           21/F       N     N      N
Poch (5)                           43/F       N     N      N
Poch (5)                           27/F       N     N      N
Poch (5)                           28/F       N     N      N
Willoughby et al. (6)              30/M       +     N      N
Yancey et al. (7)                   N         +     N      N
Yancey et al. (7)                  16/F       +     N      N
Nagaoka et al. (8)                 35/F       N     N      N
Garcia-Moreno and Chacon (9)       15/F       -     -      N
Khubchandani et al. (10)           12/F       +     +      +
Kwong et al. (11)                  9/F        +     +      +
Kwong et al. (11)                  12/F       +     +      +
Shahar et al. (12)                 15/F       +     -      +
Shahar et al. (12)                 16/F       +     -      +
Shahar et al. (12)                 12/F       +     N      N
Miyoshi et al. (13)                42/F       -     -      N
Osawa et al. (14)                  31/F       +     -      N
Lim et al. (15)                    24/M       N     +      N
Chaco'n et al. (16)                16/F       -     -      N
Tan et al. (17)                    57/F       N     +      N
Lee PH et al. (18)                 43/F             -      +
Orta Daniel and Ulises (19)        45/F       N     +      N
Our case                           17/F       N     +      N

Author                              Treatment         Outcome

Seminario and Pessano (3)               N              Death
Seminario and Pessano (3)               N              Death
Seminario and Pessano (3)               N              Death
Seminario and Pessano (3)               N              Death
Kunas et al. (4)                       APD          Improvement
Poch (5)                                N                N
Poch (5)                                N                N
Poch (5)                                G           Improvement
Poch (5)                                N                N
Willoughby et al. (6)                   G              Death
Yancey et al. (7)                       N                N
Yancey et al. (7)                       N           Improvement
Nagaoka et al. (8)                    G+APD         Improvement
Garcia-Moreno and Chacon (9)      APD+G+surgery     Improvement
Khubchandani et al. (10)            G+Cy+APD         Recovery
Kwong et al. (11)                   G+Cy+IgG         Recovery
Kwong et al. (11)                   G+Cy+IgG,        Recovery
Shahar et al. (12)                     APD           Recovery
Shahar et al. (12)                     APD          Improvement
Shahar et al. (12)                     APD               N
Miyoshi et al. (13)                     G           Improvement
Osawa et al. (14)                  G+PP+APD+Cy      Improvement
Lim et al. (15)                       G+Cy          Improvement
Chaco'n et al. (16)                    APD          Improvement
Tan et al. (17)                       G+Cy          Improvement
Lee PH et al. (18)                    G+APD          Recovery
Orta Daniel and Ulises (19)            APD          Improvement
Our case                        G+Cy+IT injection    Recovery

EEG: Electroencephalogram; MRI: Magnetic resonance imaging; SPECT:
Single-photon emission computerized tomography; N: Not done or not
Intrathecal. testable; +: Present or abnormal; -: Normal or absent;
APD: Antiparkinsonian drugs; G: Glucocorticoids; Cy: cyclophosphamide;
IgG: Immunoglobulin G; PP: Plasmapheresis; IT:
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Title Annotation:CASE REPORT
Author:Tang, Qi; Wang, Jing; Chen, Jinwei; Xie, Xi; Tian, Jing
Publication:Turkish Journal of Rheumatology
Date:Dec 1, 2015
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