Abstract
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
| Age/sex (ref) | Publication year/country | Clinical presentation | Medical history | Neurological syndromes | Disease duration | Treatment | Prognosis |
|---|---|---|---|---|---|---|---|
| 44/F (PR) | 2022/China | Involuntary movements of her right arm | Grave's disease | Normal | 1 year | Radiation (131I) therapy | Improvement within 3 months |
| 67/M (8) | 2022/Canada | Ongoing, non-distractible choreiform movements of the left upper extremity | Right frontoparietal stroke, thyroidectomy with ablation, thyroid hormone replacement | Spasticity, mildly reduced strength, and 3+ hyperreflexia/left | NR | L-thyroxine (dosage was decreased to 20 mg twice a day), beta blocker | Improvement within 2 months |
| 14/M (9) | 2021/Kenya | Chorea, tremors, a low BMI of 17 | Unremarkable | Tremor/bilateral limbs | A few months | Gabapentin, carbimazole, and radioactive iodine therapy | Improvement |
| 13/F (10) | 2020/USA | Worsening left-sided upper extremity weakness and gait unsteadiness for 1 month | Unremarkable | Tremors, gait alterations with left foot drop, slurred speech/left | 1 month | Methimazole and propranolol | Improvement within 12 months |
| 8/F(10) | 2020/Argentina | Subacute onset lost weight, gained height, involuntary movements | Asthma | Lingual fasciculations, dysarthria/bilateral limbs | 1 month | Methimazole, atenolol and carbamazepine | Improvement within 1 month |
| 62/M (11) | 2019/China | Asymmetric involuntary movement, muscle weakness, inaccurate coordinate movement, and hypomyotonia of right limbs | Diabetes, atrial fibrillation | Normal | 2 weeks | Methimazole, haloperidol, and bisoprolol | Improvement within 2 weeks |
| 60/F (12) | 2019/Switzerland | Erratic, intricate movement disorders in her left upper and lower extremities | Hypertension | Tremor/left | 5 years | Carbimazole and propylthiouracil (switched to radioiodine therapy due to severe adverse effects) | Improvement within 2 months |
| 32/F (13) | 2016/India | Jerky, non-repetitive involuntary movements of the left upper and lower limbs | Unremarkable | Normal | NR | Carbimazole | Improvement within 6 weeks |
| 25/F (14) | 2016/USA | Muscle spasms of the left shoulder and arm | Hyperthyroidism, anxiety, bipolar disorder, depression, substance abuse | Normal | NR | Metoprolol and methimazole | Improvement within 1 week |
| 60/F (15) | 2015/Switzerland | Imbalance associated with falls evolving for 5 years | Unremarkable | Normal | 5 years | Carbimazole, 131I radiotherapy | Improvement within a few weeks |
| 15/F (16) | 2013/Canada | A series of falls over the month, choreiform episodes, insomnia, fatigue, and loss of appetite | Sickle cell disease | Normal | 2 weeks | Methimazole first, then methimazole plus levothyroxine | Improvement |
| 23/F (17) | 2013/Poland | Palpitations, weight loss, and exercise intolerance | Unremarkable | Normal | NP | Thiamazole, Haloperidol, Prednisone | Improvement within 6 weeks |
| 22/F (18) | 2013/South Korea | Involuntary movement of her four extremities | Hyperthyroidism | Dysarthria | 2 months | Propylthiouracil | Improvement within 1 month |
| 16/M (19) | 2012/South Korea | Choreic movement dominant in the right limb | Unremarkable | Brisk deep tendon reflex/bilateral limbs | 9 days | Propylthiouracil, propranolol | Improvement within 8 months |
| 14/M (20) | 2012/China | Acute onset, generalized proximal muscle weakness, and hyporeflexia | Unremarkable | Normal | 5 hours | Methimazole | Improvement within 4 weeks |
| 23/F (21) | 2011/USA | Involuntary, writhing, symmetrical movements involving arms, legs, neck, tongue, and face starting 10 days following delivery of her second child. weight loss | Toxic nodular goiter | Normal | NR | Propylthiouracil, atenolol, quetiapine, and a short prednisone taper | Improvement within 6 months |
| 38/F (22) | 2010/China | Ilateral blepharospasm with visual difficulty, and facial grimacing. involuntary choreic movements in her left side | Unremarkable | Bilateral blepharospasm, oromandibular dystonia; Irregular speech in volume and tempo, irregular and unsteady gait | 3 months | Methimazole | Improvement within 4 months |
| 17/F (23) | 2009/China | Acute onset, involuntary movement of hands, forearms, feet, and face for 2 weeks | Graves' disease | Irregular and unsteady gait, irregular speech in volume and tempo | 2 weeks | Propylthiouracil, propranolol, and haloperidol | Improvement within 6 weeks |
| 42/F (24) | 2008/South Korea | Continuous, involuntary movement in her left upper extremity and face for 1 month | Graves' disease | Normal | 1 month | Methylprednisolone sodium succinate and oral antithyroid medication | Improvement |
| 19/F (25) | 2008/France | About 2 weeks before admission, she had progressively developed movement disorder, balance impairment, and dysarthria | Graves' disease | Mild dysarthria and impaired tandem walk | 2 weeks | Carbimazole and levothyroxine | Improvement within 3 months |
| 9/F (26) | 2007/USA | A 2 month-history of weight loss, hyperactivity, tremulousness, and palpitations | Unremarkable | Ataxic gait, dysmetria, and dysdiadochokinesia | 2 months | Propylthiouracil and propranolol | Improvement within 4 days |
| 78/F (27) | 2005/UK | A 1-week history of increasing agitation and worsening generalized involuntary movements | IHD, AF, AS, hypercholesterolemia, and total thyroidectomy | Impaired speech and dysphagia | 1 week | Propranolol; discontinuation of thyroxine | Improvement within 3 months |
| 50/M (6) | 2004/Yugoslavia | Sudden development of vigorous bilateral, ballistic, and severe choreic movements of all limbs, more prominent on the left side | Hyperthyroidism | Normal | NR | Haloperidol, propranolol and thiamazole | Improvement within 10 days |
| 23/F (28) | 2003/Japan | Marked sweating, irritability, poor concentration, and tremors in both hands | Parkinson's disease | Right-hand tremor | 15 months | Methimazole and β-adrenoceptor blocker | Improvement within 2 weeks |
| 24/F (29) | 1998/Japan | Acute left-sided chorea and dysarthria | Graves' disease | Normal | NR | Methimazole, propranolol, and diazepam | Improvement within 4 weeks |
| Elderly female (30) | 1994/Italy | Chorea | Hyperthyroidism | Normal | NR | - | Improvement |
| 16/F (31) | 1992/Italy | Depression of the mood, tremors, motor incoordination, and chorea more evident in the right side | Operated on for closure of a ventricular septal defect, Graves' disease | Muscular hypotonia, decreased tendon reflexes, facial grimacing, and dysarthria/right | 8 months | Methimazole | Improvement within 2 months |
| 23/F (32) | 1992/Japan | Severe involuntary movements in the left extremities | Unremarkable | Normal | 2 years | Thiamazole and propranolol | Improvement within 2 months |
Clinical characteristics of 28 patients with hyperthyroidism-associated chorea.
F, female; M, male; PR, present case; NR, not reported; IHD, ischemic heart disease; AF, atrial fibrillation; AS, aortic stenosis.
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.
Statements
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
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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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Summary
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
Volume
13 - 2022
Edited by
Alberto Albanese, Catholic University of the Sacred Heart, Italy
Reviewed by
Tommaso Ercoli, University of Cagliari, Italy; Antonella Muroni, Azienda Ospedaliero-Universitaria Cagliari, Italy; L. K. Prashanth, Vikram Hospital, India
Updates
Copyright
© 2022 Chen, Wu, An, Zheng, Zhai, Zang and Wu.
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*Correspondence: Xiaobing Wu ✉wuxb3018@163.com
This article was submitted to Movement Disorders, a section of the journal Frontiers in Neurology
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.