Abstract
Chorea is a hyperkinetic movement disorder associated with various underlyingconditions, including autoimmune diseases such as antiphospholipid syndrome (APS). APS can manifest with a wide range of neurological symptoms, including chorea. We present a case of a 77-year-old man with subacute generalized chorea secondary to primary APS. Notably, the patient exhibited a left patellar crossed-reflex, a phenomenon rarely documented in chorea cases, the pathophysiology of which has not yet been elucidated. In summary, this case challenges the traditional demographics of antiphospholipid syndrome (APS) by suggesting a potential link between APS and late-age patients. It emphasizes the importance of considering APS in late-onset chorea cases.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Chorea is a hyperkinetic movement disorder that can be caused from diverse conditions including autoimmune diseases such as antiphospholipid syndrome (APS) and also has been associated with the isolated presence of antiphospholipid antibodies (aPL) [1, 2].
APS can manifest with neurological symptoms like cerebrovascular accidents, thrombosis, seizures, and movement disorders. Although chorea's prevalence in APS is approximately 1.3%, its pathophysiological mechanisms remain unclear [1]. Postulated mechanisms include autoantibody-induced endothelial dysfunction, inflammation, and microthrombosis, or immune-mediated attack against basal ganglia epitopes [2, 3].
The presentation of chorea is usually subacute with a monophasic course and choreic movements can be focal, unilateral or generalized [3].
We present the case of a 77-year-old man with a history of atrial fibrillation anticoagulated with apixaban and severe mitral insufficiency treated with annuloplasty; who was admitted due to subacute generalized chorea (video 1, segment 1). After pharmacological control of the chorea with tetrabenazine, neurologic examination revealed the presence of a left patellar crossed-reflex that was elicited when exploring deep muscle reflexes in both the upper limbs and the contralateral half of the body (video 1, segment 2). Rest of the neurological examination was within normal limits.
Laboratory investigations revealed high serum anti B2 glycoprotein-I IgG titers (Table 1). No spinal cord or basal ganglia lesions were found in the magnetic resonance imaging (MRI, video 2), but they did find them at an extra-striatal level including periventricular white matter, right cerebellum, left thalamus and both semioval centers. HTT gene sequencing showed a CAG repeats in a normal range. Surface electromyography showed a monophasic contraction of left quadriceps (video 1, segment 3).
After etiological study, including a comprehensive neurovascular study with no other relevant findings, the patient was diagnosed as chorea secondary to primary antiphospholipid syndrome.
Tetrabenazine was started at ascending doses until tetrabenazine 12.5 mg thrice a day. The patient showed a marked improvement and at the 3 and 6-month follow-up visits, he only presented mild appendicular chorea of the left leg when performing activation maneuvers. At the one-year follow-up visit, the patient exhibited no choreic movements, and the dosage of tetrabenazine was progressively reduced until it was discontinued. He also maintains control with Hematology and in the control analyses there is a persistent increase in the titers of anti B2 glycoprotein-I IgG and the patient is undergoing anticoagulant treatment.
Discussion
Despite the fact that APS is more frequent in young female patients [1], this case in a late-age patient suggests the possible relationship with a second peak of autoimmune diseases in the context of senescence [4] which recommends the screening for APS in late-onset chorea.
Crossed-reflexes pathways in lower extremities were described more than a century ago in mice but there is no clear pathophysiologic explanation, especially for those crossed up-down limb, in humans [5]. Crossed patellar reflex with or without a polyphasic contraction pattern (hung up reflex) can be presented in other types of chorea as Huntington’s disease [6] and its pathophysiology have not been elucidated yet. Revising published literature, we did not find cases in antiphospholipid chorea.
Conclusion
This case challenges conventional assumptions about antiphospholipid syndrome (APS) by highlighting its potential association with late-age patients presenting with chorea. It underscores the significance of considering APS in the differential diagnosis of late-onset chorea cases. Furthermore, the intriguing presence of crossed-reflexes, exemplified by the left patellar crossed-reflex in this case, raises questions about their pathophysiology in chorea, an area that warrants further investigation.
References
Lerjefors L, Andretta S, Bonato G, Mainardi M, Carecchio M, Antonini A. Antiphospholipid-Related Chorea: Two Case Reports and Role of Metabolic Imaging. Mov Disord Clin Pract. 2022;9(4):516–521. Published 2022 Mar 28. https://doi.org/10.1002/mdc3.13432
Farag M, Hunt BJ, Andrews TC (2023) Antiphospholipid-related chorea. Pract Neurol 23(2):150–152. https://doi.org/10.1136/pn-2022-003587
Peluso S, Antenora A, De Rosa A et al (2012) Antiphospholipid-related chorea. Front Neurol. 2012;3:150. Published. https://doi.org/10.3389/fneur.2012.00150
Ray, Donna, and Raymond Yung (2018) “Immune senescence, epigenetics and autoimmunity.” Clinical immunology (Orlando, Fla.) 196: 59–63. https://doi.org/10.1016/j.clim.2018.04.002
Laflamme, Olivier D, and Turgay Akay (2018) “Excitatory and inhibitory crossed reflex pathways in mice.” Journal of neurophysiology vol. 120,6: 2897–2907. https://doi.org/10.1152/jn.00450.2018
J. Perez-Perez, J. Diaz-Manera, J. Pagonabarraga, S. Martinez-Horta, M. Carceller, A. Horta, J. Marin, H. Bejr-Kasen, A. Guerrero, J. Kulisevsky. Hung up knee jerk reflex in Huntington’s disease: A clinical and neurophysiological study [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/hung-up-knee-jerk-reflex-in-huntingtons-disease-a-clinical-and-neurophysiological-study/
Funding
Open Access Funding provided by Universitat Autonoma de Barcelona.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical statement
This report, inclusive of a patient video, upholds confidentiality and secured informed consent. It complies with ethical standards, prioritizing medical advancement while safeguarding patient privacy.
Conflicts of interest
The authors declare that there is no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Supplementary file1 (MP4 9.78 MB)
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Fernández-Vidal, J.M., Olmedo-Saura, G., Querol-Gutiérrez, L.A. et al. Crossed-reflex in antiphospholipid chorea. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07622-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10072-024-07622-5