Hemichorea–hemiballism is a spectrum of involuntary, non-patterned movement involving one side of the body. It usually results from a lesion in the contralateral basal ganglia structure, but it is also a well-recognized complication of several conditions, including non-ketotic hyperglycemia and polycythemia vera.1
Although induced parkinsonisms and other hyperkinetic movement disorders are repeatedly reported with selective serotonin reuptake inhibitors (SSRIs),2,3 drug-induced hemichorea has rarely been reported4–9 (Table 1). Herein we report a case of hemichorea induced by sertraline. To the best of our knowledge, no previous cases of sertraline-induced hemichorea have been reported in the literature.
|Sex/Age (years)||History||Hemichorea||Brain MRI||Drug||Mechanism of Action||References|
|M/41||None||Right||Normal||Gabapentin||Binds to many transmembrane sites within the central nervous system embracing the α-2-δ subunit of the voltage-gated calcium||Lai et al.8|
|F/76||Alzheimer disease||Right upper limbDystonia left lower limb||NA||Memantine||Non-competitive antagonist of NMDA receptor, dopaminergic action at high doses||Borges et al.4|
|F/92||Hypertension||Right||Normal||Zolpidem/zopiclone||Agonist GABA A||Watari and Tokuda5|
|F/17||Irregular menstrual cycle||Right||NA||Oral contraceptive pills (ethinyl estradiol and cyproterone acetate)||Competitive inhibition of the binding of testosterone and dihydrotestosterone to androgen receptorsDopaminergic action at high doses||Sharmila and Babu6|
|M/53||HypertensionRight frontal hemorrhage||Left||Right frontal hemorrhage||Valproate||Inhibitory GABA, excitatory NMDA receptor and sodium channel pathways||Srinivasan and Lok9|
|F/65||Depression||Left||Normal||Sertraline||Selective serotonin reuptake inhibitor||Present case, 2017|
A 65-year-old right-handed Argentinean female was diagnosed with depression and was started on sertraline 50 mg per day. One week later, she developed involuntary movements involving the left upper and lower limbs.
Twenty-four hours later she was admitted into our institution. Physical examination revealed hemichorea on the left side, but the rest of the neurological and clinical examination, including the Mini Mental Status Examination, was unremarkable.
The patient’s past medical history included smoking (more than 40 cigarettes/day), hiatus hernia, and irritable bowel syndrome. She had no other significant disorders involving the central, peripheral, or autonomic nervous systems. Her family history was non-contributory and no additional medications were taken in the previous 6 months, even for irritable bowel syndrome.
A 1.5 Tesla brain magnetic resonance imaging scan including diffusion-weighted images and magnetic resonance angiography (MRA) was performed 48 hours after the initial symptoms, and no acute lesions or relevant abnormalities were identified (Figure 1). Routine blood tests demonstrated no abnormalities in the full blood count (hemoglobin, 13.2 g/dL; hematocrit, 39.20%) and liver or renal function. Thyroid function, blood glucose, calcium, magnesium, phosphate, serum ceruloplasmin, vitamin D, and parathyroid hormone levels were all normal. Serum carcinoembryonic antigen, cancer antigen (CA) 15.3, CA 19.9, CA 125, paraneoplastic antibodies (anti-Yo, anti-Hu, anti-Ri), p-Antinuclear and anticytoplasmic antibodies (ANCA) and c-ANCA, anti-transglutaminase, anti-gliadin, and anti-endomysium antibodies, anti-nuclear antibody, anti-cardiolipin antibody, and HIV serology were negative. To exclude other systemic causes, chest, abdominal, and pelvic computed tomography (CT) scans were performed, which were normal. Carotid ultrasound, echocardiogram, and upper and lower endoscopy were normal.
Cerebrospinal fluid analysis was unremarkable, and onconeural antibodies were negative (anti-Yo, anti-Hu, anti-Ri, anti-N-methyl-D-aspartic acid receptor, anti-Antiglutamate receptor (AMPA subtype1), anti-Antiglutamate receptor (AMPA subtype2), anti-Contactin associated protein 2 (CASPR2), anti-Leucine rich glioma inactivated 1 (LGI 1), gamma-aminobutyric acid B-receptor (GABAB-R), collapsin response mediator protein 5 (CRMP5)). As no other etiologic agents were identified, sertraline was discontinued and the involuntary movements gradually disappeared over 7 days.
The patient was diagnosed with a probable sertraline drug-induced hemichorea. See video, segment 1: basal examination, segment 2: evaluation one month after initial presentation and sertraline withdrawal.
We present a patient with hemichorea related to sertraline therapy. Sertraline is a SSRI, commonly used in depression.10 According to the pharmaco-epidemiological data by the US Food and Drug Administration, only 10% of all SSRI-induced movement disorders have been reported to be secondary to sertraline,11 particularly in those cases with concomitant medications.11,12
The most common movement disorders induced by sertraline included tremor, dystonia, and akathisia.12 However, to the best of our knowledge, no previous chorea or hemichorea cases associated with sertraline have been previously reported.
The mechanism by which SSRI could induce movement disorders remains to be elucidated.13 Two possible mechanisms have been proposed. The first suggested that sertraline is able not only to inhibit serotonin reuptake but also to exert a mild dopaminergic inhibition in the ventral tegmental area and nigrostriatal pathway.14 The second hypothesis proposed a genetic mechanism involving serotonin or dopamine receptor polymorphisms or cytochrome P450 phenotypes.15 These two hypotheses may explain the usually bilateral acute or tardive symptoms; however, it remains to be elucidated why hemichorea rather than generalized chorea occurred in this case.
Several concomitant and previous conditions could contribute to increase the susceptibility for developing hemichorea. In our patient we ruled out chorea gravidarum, post-streptococcal chorea, autoimmune-mediated hemichorea, polycythemia vera, and vascular and structural causes, among others.1
While in this case a personal history of smoking could be observed as a risk factor for hemichorea development, in the literature only one case of smoking was reported as a worsening and non-primary causal factor in a 65-year-old hypertensive male with a right putamen hemorrhage.16 In our patient, smoking did not seem to be involved in the pathogenesis of the hemichorea. Therefore, the acute appearance of hemichorea and the recent administration of sertraline, after excluding other possible causes of acquired hemichorea, suggest a probable drug-induced mechanism.
Although the extended use of sertraline revealed a safe profile in daily doses ranging from 50 to 200 mg, it is important to keep in mind that this drug may induce hemichorea, albeit very rarely.
1 Funding: None.
2 Financial Disclosures: None.
3 Conflicts of Interest: The authors report no conflict of interest.
4 Ethics Statement: All patients that appear on video have provided written informed consent; authorization for the videotaping and for publication of the videotape was provided.
The authors would like to thank the patient for her participation and collaboration.
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Sharmila, V and Babu, TA (2015). Oral contraceptive pills induced hemichorea in an adolescent female with polycystic ovarian disease. Indian J Pharmacol 47: 232–233. doi: 10.4103/0253-7613.153440. [PubMed]
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