You're viewing our updated article page. If you need more time to adjust, you can return to the old layout.

CASE REPORT article

Front. Neurol., 22 December 2022

Sec. Movement Disorders

Volume 13 - 2022 | https://doi.org/10.3389/fneur.2022.1074156

Unilateral upper limb chorea associated with hyperthyroidism: A case report and literature review

    WC

    Wei Chen

    BW

    Bin Wu

    HA

    Hongna An

    KZ

    Kaiying Zheng

    DZ

    Daming Zhai

    JZ

    Jiahua Zang

    XW

    Xiaobing Wu *

  • Department of Neurology, The Second People's Hospital of Quzhou, Quzhou, China

Article metrics

View details

4

Citations

3,8k

Views

917

Downloads

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

References

  • 1.

    Burn D . Oxford Textbook of Movement Disorders. London: BMJ Publishing Group Ltd. (2015).

  • 2.

    Talukder P Jana A Dhar S Ghosh S . Huntington's chorea-a rare neurodegenerative autosomal dominant disease: insight into molecular genetics, prognosis and diagnosis. Appl Biochem Biotechnol. (2021) 193:263448. 10.1007/s12010-021-03523-x

  • 3.

    Sasaki T Suzuki Y Sato M . Hyperglycemic chorea. Oxf Med Case Rep. (2021) 2021:omab118. 10.1093/omcr/omab118

  • 4.

    Laban T Larroche C Comparon C Dhote R Degos B . Fluoxetine-induced chorea. Rev Neurol. (2021) 177:10101. 10.1016/j.neurol.2020.12.007

  • 5.

    Bovenzi R Conti M Cerroni R Pierantozzi M Stefani A Pisani A et al . Adult-onset sporadic chorea: real-world data from a single-centre retrospective study. Neurol Sci. (2021) 43:38792. 10.1007/s10072-021-05332-w

  • 6.

    Ristić AJ Svetel M Dragasević N Zarković M Koprivsek K Kostić VS . Bilateral chorea-ballism associated with hyperthyroidism. Mov Disord. (2004) 19:9823. 10.1002/mds.20119

  • 7.

    WR G . A manual of the diseases of the nervous system. JAMA. (1893) xxi:950. 10.1001/jama.1893.02420770040013

  • 8.

    Lun R Moores M Mestre T Breiner A . Thyrotoxicosis resulting in unilateral upper limb chorea and ballismus. Can J Neurol Sci. (2022) 49:4312. 10.1017/cjn.2021.136

  • 9.

    Mongare N Njenga E Sokhi D . Medically refractory Graves' disease presenting as chorea and carbohydrate hyperphagia in a Kenyan adolescent. Mov Disord. (2021) 36(SUPPL 1):S25.

  • 10.

    Vundamati D Tsai S . Simultaneous onset of autoimmune hyperthyroidism and rheumatic fever in an adolescent female-case report. US Endocrinol. (2020) 16:1258. 10.17925/USE.2020.16.2.125

  • 11.

    Li X Wang R He J Xu L . Unilateral chorea secondary to hyperthyroidism: a case report. Int J Clin Exp Med. (2019) 12:78703.

  • 12.

    Delhasse S Debove I Arnold-Kunz G Ghika JA Chabwine JN . Erratic movement disorders disclosing Graves' disease and paralleling thyroid function but not autoantibody levels. J Int Med Res. (2019) 47:137886. 10.1177/0300060518816873

  • 13.

    Raghavendra Rao S Seshadri S Karthik Rao N Patil N Kunder SK Avinash A . Hemichorea: an unusual manifestation of thyrotoxicosis. Asian J Pharm Clin Res. (2016) 9.

  • 14.

    Arifi B Gupta S Sharma S Daraboina A Ahuja S . A case report of chorea associated with hyperthyroidism. J Clin Diagn Res. (2016) 10:PL01. 10.7860/JCDR/2016/17299.7277

  • 15.

    Delhasse S Debove I Ghika JA Chabwine JN . Erratic movement disorders disclosing Grave's disease. Schweiz Arch Neurol Psychiatr. (2015) 166(Supplement 7):66.

  • 16.

    Leblicq C Duval M Carmant L Van Vliet G Alos N . Rising serum thyroxine levels and chorea in graves' disease. Pediatrics. (2013) 131:e6169. 10.1542/peds.2012-0686

  • 17.

    Kaminska A Kaminski M Nowaczewska M Ksiazkiewicz B Junik R . Chorea, convulsive seizures and cognitive impairment in a patient with autoimmune thyroid disease. Neurol Sci. (2013) 34:2634. 10.1007/s10072-012-0990-4

  • 18.

    Chung EJ Bae SK Kim SJ . Generalized chorea with abnormal 18F-fluorodeoxyglucose positron emission tomography findings in a patient with hyperthyroidism. Clin Neurol Neurosurg. (2013) 115:1089. 10.1016/j.clineuro.2012.04.031

  • 19.

    Park J Kim JG Park SP Lee HW . Asymmetric chorea as presenting symptom in Graves' disease. Neurol Sci. (2012) 33:3435. 10.1007/s10072-011-0679-0

  • 20.

    Nakavachara P Suppakrucha M Likasitwattanakul S . Thyrotoxic periodic paralysis and chorea: two uncommon neuromuscular complications in an adolescent with newly diagnosed Graves disease. In: International Journal of Pediatric Endocrinology Conference: 7th Asia Pacific Paediatric Endocrine Society Biennial Scientific Meeting, APPES. (2012). 10.1186/1687-9856-2013-S1-P145

  • 21.

    Masannat Y Gandhy R Olajide O Kheetan R Yaqub A . Chorea associated with thyrotoxicosis due to toxic multinodular goiter. Thyroid. (2011) 21:127980. 10.1089/thy.2011.0018

  • 22.

    Miao J Liu R Li J Du Y Zhang W Li Z . Meige's syndrome and hemichorea associated with hyperthyroidism. J Neurol Sci. (2010) 288:1757. 10.1016/j.jns.2009.10.018

  • 23.

    Yu JH Weng YM . Acute chorea as a presentation of Graves disease: case report and review. Am J Emerg Med. (2009) 27:369.e13. 10.1016/j.ajem.2008.05.031

  • 24.

    Ku CR Park HJ Hong SJ Shin DY Lee JH Chung MJ et al . A case of Graves' disease presenting with Chorea. Endocrinol Metab. (2008) 23:3426. 10.3803/jkes.2008.23.5.342

  • 25.

    Garcin B Louissaint T Hosseini H Blanc R Fenelon G . Reversible chorea in association with Graves' disease and moyamoya syndrome. Mov Disord. (2008) 23:6202. 10.1002/mds.21941

  • 26.

    Seeherunvong T Diamantopoulos S Berkovitz GD . A nine year old girl with thyrotoxicosis, ataxia, and chorea. Brain Dev. (2007) 29:6601. 10.1016/j.braindev.2007.04.002

  • 27.

    Isaacs JD Rakshi J Baker R Brooks DJ Warrens AN . Chorea associated with thyroxine replacement therapy. Mov Disord. (2005) 20:16567. 10.1002/mds.20603

  • 28.

    Hayashi R Hashimoto T Tako K . Efficacy of propranolol in hyperthyroid-induced chorea: a case report. Mov Disord. (2003) 18:10736. 10.1002/mds.10477

  • 29.

    Nagaoka T Matsushita S Nagai Y Kobayashi K . A woman who trembled, then had chorea. Lancet. (1998) 351:1326. 10.1016/S0140-6736(97)11126-6

  • 30.

    Lucantoni C Grottoli S Moretti A . Chorea due to hyperthyroidism in old age. A case report. Acta Neurol. (1994) 16:12933.

  • 31.

    Pozzan GB Battistella PA Rigon F Zancan L Casara GL Pellegrino PA et al . Hyperthyroid-induced chorea in an adolescent girl. Brain Dev. (1992) 14:1267. 10.1016/S0387-7604(12)80102-1

  • 32.

    Baba M Matsunaga M Terada A Hishida R Takebe K Kawabe Y et al . Persistent hemichorea associated with thyrotoxicosis. Intern Med. (1992) 31:11446. 10.2169/internalmedicine.31.1144

  • 33.

    Waldenström J . Acute thyrotoxic encephalo- or myopathy, its cause and treatment. Acta Med Scand. (1945) 121:25194. 10.1111/j.0954-6820.1945.tb06882.x

  • 34.

    Klawans HL Shenker DM . Observations on the dopaminergic nature of hyperthyroid chorea. J Neural Transm. (1972) 33:7381. 10.1007/BF01244729

  • 35.

    Baba M Terada A Hishida R Matsunaga M Kawabe Y Takebe K . Persistent hemichorea associated with thyrotoxicosis. Intern Med. (1992) 31:11446. 10.2169/internalmedicine.31.1144

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

*Correspondence: Xiaobing Wu ✉

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.

Outline

Cite article

Copy to clipboard


Export citation file


Share article

Article metrics