Short abstract
https://onlinelibrary.wiley.com/page/journal/23301619/homepage/mdc312943-sup-v001.htm
Movement disorders are uncommon neuropsychiatric manifestations of systemic lupus erythematosus (SLE).1 Chorea is the most common movement disorder described in SLE, followed by parkinsonism, tremor, and myoclonus. Other rare movement disorders associated with SLE include dystonia (torticollis and blepharospasm) and ataxia. The pathophysiological mechanisms of movement disorders in SLE are unclear, but are presumed to be related with basal ganglia involvement. For instance, if associated with antiphospholipid antibody syndrome, probably it has an underlying mechanism that involves antibody‐mediated endothelial dysfunction, microthrombosis, and neuroinflammation at this topography.2
Herein, we describe a patient with SLE who presented with acute parkinsonism and unusual imaging changes. Serial MRI revealed significant improvement as well as complete neurological recovery.
Case Report
A 20‐year‐old man presented with a 1‐week history of gait disturbance, cognitive changes, and urinary incontinence. For the past 2 weeks, he presented with behavior changes, apathy, and emotional lability. There was also chest pain and pleural effusion. Four months before, he reported arthralgia, lower‐limb edema, bilateral malar rash, anorexia with significant weight loss, and evening fever with sweating. Neurological examination disclosed cognitive impairment (mental confusion, bradipsychism, and apathy), slurred speech, dysphagia, frontal release signs (glabelar, snout, and grasping reflexes), and marked parkinsonism characterized by freezing of gait, postural instability, bradykinesia, and global rigidity (Video 1). Brain MRI showed bilateral and symmetrical T2 and fluid‐attenuated image recovery (FLAIR) hyperintense signal in periventricular white matter, semioval centers, and internal capsule with extension to the corticospinal tract with restricted diffusion and no contrast enhancement (Fig. 1). MRI angiography ruled out vasculitis. A brain dopamine transporter (DAT) imaging using single‐photon emission computer tomography (SPECT) and TRODAT‐1 disclosed normal striatal DAT within the striatum. Serologies and cerebrospinal fluid (CSF) exams were normal. Other additional tests showed: anemia; undetectable total complement and C2; positive antinuclear antibodies (≥1:280, homogeneous nuclear); anti‐DNA (≥1:320); and positive antiribonucleoprotein and positive anti‐Sm. An onconeural antibodies panel performed in serum and CSF was negative. SLE was diagnosed based on Systemic Lupus International Collaborating Clinics criteria with a Systemic Lupus Erythematosus Disease Activity Index‐2K of 33. He was treated with a combination of intravenous methylprednisolone 1 g daily for 5 days, followed by intravenous cyclophosphamide. Levodopa 800 mg daily was also started. The patient presented with a marked improvement in neurological symptoms, and the video performed 1 month after immunotherapy showed a complete improvement of the parkinsonism (Video 1). A follow‐up brain MRI also showed a marked improvement (Fig. 1). Prednisone 80 mg daily and azathioprine 150 mg daily were started, and l‐dopa was discontinued because patient improved with immunotherapy. A 1‐year follow‐up disclosed no neurological symptoms.
Figure 1.
(A,B) Axial FLAIR‐weighted brain MRI shows symmetrical bilateral hyperintense signal affecting periventricular white matter, semioval centers, and internal capsule with an extension to the corticospinal tract. (C) Sagittal T1‐weighted brain MRI discloses hypointense signal in pyramidal tracts. (D) A brain DAT imaging using SPECT and TRODAT‐1 disclosed normal striatal DAT within the striatum.
Discussion
This is a rare case of acute parkinsonism in SLE associated with encephalopathy, that presented a marked response to immunotherapy, which suggests an immune‐mediated pathophysiological mechanism. Interestingly, brain MRI also showed periventricular white matter abnormalities and a symmetrical hyperintense signal in semioval centers and internal capsule, which are also very unusual changes in SLE.
Acute parkinsonism is usually related to secondary causes, such as dopamine receptor‐blocking drugs (neuroleptics), inflammatory diseases that affect basal ganglia (viral, bacterial, or fungal encephalitis), and poisoning (carbon monoxide, cyanide, and methanol).3 Other unusual causes of acute parkinsonism include arterial occlusion, extrapontine myelinolysis, neuro‐Behçet, toxoplasmosis, and primary central nervous system lymphoma.3
The pathophysiological mechanisms of parkinsonism in SLE are unclear. In this report, vasculitis was ruled out, and an immune‐mediated mechanism was the most likely explanation. Considering that brain TRODAT‐1 was normal, we can state that the presynaptic dopaminergic pathway was preserved, but other pathways, postsynaptic or synaptic dopaminergic pathways, or even nondopaminergic pathways, may be involved. Marino et al. reported a similar case of a woman that presented with 1‐month history of parkinsonism and laboratory findings of SLE. In this report, brain MRI showed hyperintense signal in T2/FLAIR‐weighted images, and brain SPECT with dopamine transporter was normal, like our report.4
For the past decades, several onconeural antibodies have been described in autoimmune encephalitis, and parkinsonism may be observed in some forms.5 Paraneoplastic striatal encephalitis is associated with the presence of CV2/CRMP5, Ri, Ma2, and/or Hu antibodies, and the disabling disease course is a red flag.6 Encephalitis without underlying neoplasm, such as related with leucine‐rich glioma‐inactivated 1, dipeptidyl‐peptidase‐like protein 6, and glutamic acid decarboxylase antibodies, could also manifest with parkinsonism. In children and young adults, especially if associated with behavior change, the differential diagnosis must include tests for N‐methyl‐D‐aspartate receptor and dopamine receptor 2 antibodies.7 In our patient, the onconeural antibodies panel performed in serum and CSF was negative.
There are few cases of parkinsonism in SLE.8 Kwong et al. reported on 2 patients with SLE who developed parkinsonian features, which presented poor response with methylprednisolone and cyclophosphamide, but had a complete recovery with intravenous immunoglobulin.9 Tang et al. reported on a 17‐year‐old patient with parkinsonism and SLE with no response with methylprednisolone and cyclophosphamide, but had a marked improvement with intrathecal injection of methotrexate and dexamethasone.10
In conclusion, this instructive and unusual case report shows that acute parkinsonism should direct diagnosis to SLE, and that neurological symptoms improve after immunotherapy. Furthermore, we showed that the presynaptic pathway is preserved and presume an immune‐mediated pathophysiological mechanism as the most likely explanation. Finally, in patients with SLE, an MRI follow‐up may demonstrate a complete recovery of brain abnormalities in immune‐mediated parkinsonism.
Author Roles
(1) Case Report Project: A. Conception, B. Organization, C. Execution; (2) Manuscript: A. Writing of the First Draft, B. Review and Critique.
M.P.M.M.: 1A, 1B, 1C, 2A, 2B
R.P.A.S.: 1A, 1B, 1C, 2A, 2B
A.C.F.: 1A, 1B, 1C, 2A, 2B
F.F.A.: 1A, 1B, 1C, 2B
O.G.P.B.: 1A, 1B, 1C, 2B
Disclosures
Ethical Compliance Statement
Full consent was obtained from the patient for the case‐report publication that was approved by the Ethics Committee of Federal University of Sao Paulo as protocol number 0491/2017. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest
The authors report no sources of funding and no conflicts of interest.
Financial Disclosures for previous 12 months
The authors declare that there are no disclosures to report.
Supporting information
Video 1. Patient with SLE presenting with acute parkinsonism, characterized by severe freezing of gait, bradykinesia, and hypomimia. One month after immunotherapy, there was a complete improvement in parkinsonism, and the patient presented with a normal gait.
Relevant disclosures and conflicts of interest are listed at the end of this article.
A video accompanying this article is available in the supporting information here.
[Correction made 29 April 2020. Figure 1 included an incorrect patent MRI and has been updated.]
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Associated Data
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Supplementary Materials
Video 1. Patient with SLE presenting with acute parkinsonism, characterized by severe freezing of gait, bradykinesia, and hypomimia. One month after immunotherapy, there was a complete improvement in parkinsonism, and the patient presented with a normal gait.