Wei Chen
Bin Wu- Department of Neurology, The Second People's Hospital of Quzhou, Quzhou, China
Chorea, a hyperkinetic syndrome, is generally reported in patients with Huntington's disease (HD), hyperglycemia, and other diseases but occasionally occurs in patients with Grave's disease. Here, we report a 44-year-old woman presenting with a 1-year history of involuntary movements with a known history of primary hyperthyroidism. Physical examination revealed the continuous, rapid, irregular, and spontaneous choreic movement of her right arm. Laboratory investigations demonstrated increased triiodothyronine (T3) and free thyroxine (FT4) and suppressed thyroid-stimulating hormone (TSH) levels. An electroencephalogram and brain magnetic resonance imaging were normal. After antithyroid treatment, the patient achieved complete remission. Our case indicated that hemichorea might initially manifest hyperthyroidism. Therefore, thyroid function tests should be routinely performed in patients with chorea.
Introduction
Chorea is a hyperkinetic syndrome characterized by irregular, brief and non-stereotyped movements resulting from abrupt twitching of the muscles, which flit from one body region to another (1). Chorea is commonly described in patients with Huntington's disease (HD) (2), hyperglycemia (3), autoimmune thyroid disease, drug toxication (4), etc. (5). However, chorea is a rare complication of hyperthyroidism, with <2% of chorea cases occurring in patients with Grave's disease (6). In this report, we present a case of hemichorea as the first manifestation of hyperthyroidism which was resolved with antithyroid therapy.
The study was performed according to the principles of the Helsinki declaration and the local ethical standards. Written informed consent was obtained from the patient.
Case report
A 44-year-old female patient was admitted to our neurology department in October 2021 due to a one-year history of involuntary movements of her right arm. She had been diagnosed with uncontrolled hyperthyroidism due to Grave's disease in April 2021 and treated with methimazole (10 mg daily). There was an obvious improvement in her involuntary movements 1 month later, but she had to stop taking methimazole due to the development of urticarial and liver dysfunction. She has not received other antithyroid drugs or radioiodine treatment for hyperthyroidism.
After the discontinuation of methimazole, her involuntary movements gradually deteriorated, with symptoms occurring at any time, even during sleep. In addition, she complained of mild palpitations, irritability, and anxiety. By the time of admission, the choreiform movements were continuous, rapid, irregular, and spontaneous (Supplementary Video S1), and her right arm was totally out of control. She had lost weight and had a rapid heart rate of 126 beats per minute. Neurological examination was otherwise normal except for choreic movements predominating in the right upper limb.
Laboratory results revealed increased triiodothyronine (T3) level (8.26 nmol/L, normal range: 0.92–2.79 nmol/L) and free thyroxine (FT4) level (58.13 pmol/L, normal range: 11.50–22.70 pmol/L), suppressed thyroid-stimulating hormone (TSH) level (<0.01 mIU/L, normal range: 0.55–4.78 mIU/L), and a positive anti-thyroglobulin antibody titer (105.20 KIU/L, normal range: 0–60.00 KIU/L). Hematologic investigations, including a complete blood cell count, liver and kidney functions, glucose level, autoantibody titers, serum tumor markers, ceruloplasmin, and creatine kinase activity, were normal. Thyroid ultrasonography showed diffuse heterogeneity, focal hypoechogenicity of the thyroid gland, and a diffusely enhanced thyroid blood flow. The electroencephalogram was within normal limits. Brain magnetic resonance imaging (MRI) showed normal axial T1, T2, and DWI. Lumbar puncture confirmed normal opening pressure, and no abnormality was observed in the cerebrospinal fluid analysis.
Considering her methimazole intolerance, she was treated with radiation (131I) therapy. Her symptoms gradually resolved (Supplementary Video S2), along with slightly decreased T3 and T4 and elevated TSH levels. The chorea movement almost disappeared 3 months later, and there was no recurrence after 6 months of follow-up.
Literature review and discussion
This unusual case of hemichorea secondary to hyperthyroidism was resolved with a (131I) regimen. Chorea is an abnormal movement disorder typically manifesting as continual involuntary, abrupt, rapid, brief, and irregular movements that randomly flow from one body part to another in a non-stereotyped mode. In rare instances, chorea is related to poorly controlled hyperthyroidism, which was first reported by Gowers in 1983 (7).
We reviewed case reports of hyperthyroid-related chorea published between January 1990 and August 2022, identifying 27 cases of chorea due to hyperthyroidism. The clinical characteristics of all 28 cases, including our case, are presented in Table 1. The median age of patients with hyperthyroid chorea was 23 years old (range, 8–78 years) and was reported in 22 females (77.8%) and six males, five from China, four from the United States, three from Japan, and three from South Korea. Hyperthyroid-related chorea is typically manifested by acute or subacute and progressive choreiform movements with predominant distal involvement. The involuntary movements symmetrically (17 cases) or asymmetrically involve arms and legs, predominating on the left side (11 cases), and are more pronounced in the leg while walking, causing infrequent falls. The trunk, face, and bucco-oral-lingual region can also be affected, resulting in speech disturbance and dysphagia. Thyrotoxic symptoms, including weight loss, palpitations, sweating, and anxiety, usually appear weeks to years before involuntary movements. Neurological examinations are commonly normal, but some cases reported brisk deep tendon reflexes. The characteristics of hyperthyroid chorea on neuroimaging, including CT, MRI, and MRA of the brain, were normal, and the brain MRI and MRA of the current case also revealed no structural changes. In our case, the patient presented with acute onset of worsening involuntary movements of her right arm.
Table 1. Clinical characteristics of 28 patients with hyperthyroidism-associated chorea.
To date, the physiopathologic mechanisms of hyperthyroid-related chorea remain elusive. It has been suggested that chorea may result from a direct effect of thyrotoxicosis on the central nervous system in Graves' disease. Structural changes in the basal ganglia have not been demonstrated postmortem (33), which is consistent with the normal neuroimaging of the previously reported cases. Hypersensitivity of the dopaminergic system in the nigrostriatal pathway of basal ganglia has been suggested to be one of the underlying mechanisms. Homo-vanillic acid, a dopamine metabolite, was significantly decreased in the cerebrospinal fluid of hyperthyroid patients (34). Moreover, treatment with dopamine antagonists can alleviate the symptoms of hyperthyroidism-related chorea (35). Functional modification of adrenergic receptors may also be involved in hyperthyroid-related chorea (14, 28), which is also supported by the partially relieved chorea with propranolol (a non-selective β1 and β2 adrenergic receptor blocker) treatment. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed elevated metabolism in the bilateral basal ganglia in a patient whose choreic movements predominately involved her right side (18), suggesting that hyperthyroidism may have a direct thyrotoxicosis effect resulting in excessive dopaminergic activity in the basal ganglia.
Treating hyperthyroidism-associated chorea consists of correcting thyroid function with antithyroid drugs and adding symptomatic agents, if necessary. In most patients, the choreic movements gradually improved over weeks or months with the normalization of their thyroid function. Although some patients must stop the antithyroid drug because of adverse effects such as severe muscle pain and myalgia, significant clinical alleviation was noticed in parallel with their improved thyroid function. These patients also benefited from radioiodine or thyroidectomy. Hence, it is indicated that hyperthyroidism-associated chorea is reversible after treatment with beta-adrenergic blockers, dopamine antagonists, and especially antithyroid drugs.
Conclusion
In summary, hemichorea is rare in hyperthyroidism patients and may be the initial manifestation of hyperthyroidism. Therefore, it is recommended that thyroid function tests should be routinely performed in patients with chorea. The rapid resolution of the chorea after controlling the hyperthyroidism in the absence of any structural lesion suggests that the movement disorder was likely a result of thyrotoxicosis-induced biochemical changes rather than the coexistence of a structural lesion. Further studies are needed to explore the etiology and pathogenesis of hyperthyroidism-induced chorea.
Data availability statement
The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.
Ethics statement
The studies involving human participants were reviewed and approved by the Ethical Committee of the Second People's Hospital of Quzhou. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
WC designed the work and wrote the original draft. WC, BW, HA, KZ, DZ, JZ, and XW initiated the project, collected, and analyzed the data. XW wrote the review, edited, supervised, and validated the manuscript. All authors read and approved the final manuscript.
Acknowledgments
The authors would like to express their gratitude to the patient.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
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Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2022.1074156/full#supplementary-material
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Keywords: chorea, involuntary movement, hyperthyroidism, Graves' disease, initial presentation
Citation: Chen W, Wu B, An H, Zheng K, Zhai D, Zang J and Wu X (2022) Unilateral upper limb chorea associated with hyperthyroidism: A case report and literature review. Front. Neurol. 13:1074156. doi: 10.3389/fneur.2022.1074156
Received: 19 October 2022; Accepted: 06 December 2022;
Published: 22 December 2022.
Edited by:
Alberto Albanese, Catholic University of the Sacred Heart, ItalyReviewed by:
Tommaso Ercoli, University of Cagliari, ItalyAntonella Muroni, Azienda Ospedaliero-Universitaria Cagliari, Italy
L. K. Prashanth, Vikram Hospital, India
Copyright © 2022 Chen, Wu, An, Zheng, Zhai, Zang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xiaobing Wu, 
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