Ischemic strokes in the structure of neurological disorders in children with linear scleroderma of the head

Objective. The aim of the study: analysis of the structure of neurological disorders in children with linear scleroderma of the head.

Methods. Clinical and neurological observation, MRI, EEG, examination of genetic thrombophilia markers.

Results. A total of 60 patients with linear scleroderma of the face and head (LSF) were examined: 23 boys (38.33%) and 37 girls (61.67%) aged between 3 and 16 years. The average age of disease onset was 6.64 ± 0.53 years. Neurological disorders were found in half of the patients (n = 32; 51.67%). Among them, disease onset in 26 children (81.3%) was characterized by typical skin changes, while in 8 (25%) it was characterized by neurological signs. Neurological disorders included headaches (in 43.8% of children), epileptic seizures (in 25%), cranial nerve involvement, acute cerebrovascular disorders (9.4%), and tics (9.4%). MRI of the brain revealed changes in 27 out of 32 children with neurological disorders (84%): white matter lesions (63%) and less commonly gliotic changes in the periventricular area (31%). EEG monitoring detected abnormalities in 21 children (65%), but a typical pattern of epileptiform activity was only found in 14 children (24%), including 6 children (10% of cases) with epileptiform activity without clinical seizures. Among the three children with acute cerebrovascular disorders, all were diagnosed with genetic thrombophilia, two had cerebral vascular malformations, and one had antiphospholipid syndrome.

Conclusion. The pathogenesis of strokes in children with LSF involves sclerodermic vasculopathy, cerebral vascular anomalies, and mutations in blood coagulation genes leading to hypercoagulability.

1. Zulian F., Athreya B. H., Laxer R., et al. Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study. Rheumatology (Oxford). 2006; 45 (5): 614-20. DOI: 10.1093/rheumatology/kei251. Epub 2005 Dec 20. PMID: 16368732 DOI: 10.1093/rheumatology/kei251.

2. Ayşe Akbaş, Fadime Kılınç, Yıldız Hayran. A Comparison of Clinical, Demographic and Treatment Characteristics of Pediatric-Onset and Adult-Onset Patients Diagnosed With Localized Scleroderma. Dermatol Pract Concept. 2024; 14 (1): e2024023. DOI: 10.5826/dpc.1401a23.

3. Nguyen K., Atty C., Ree A. Linear scleroderma en coup de sabre presenting with seizures. Radiol Case Rep. 2020; 15 (11): 2164-2170. Published online 2020 Sep 3. DOI: 10.1016/j.radcr.2020.08.011.

4. Tasleem Arif, Rafiya Fatima, Marwa Sami. Parry-Romberg syndrome: a mini review. Acta Dermatovenerol APA. 2020; 29: 193-199. DOI: 10.15570/actaapa.2020.39.

5. Yvonne E., Chiu M. D., Sheetal Vora M. D., Eun-Kyung M. Kwon B. A., et al. A Significant Proportion of Children with Morphea En Coup De Sabre and Parry-Romberg Syndrome Have Neuroimaging Findings. Pediatr Dermatol. 2012; 29 (6): 738-748. DOI: 10.1111/pde.12001.

6. Yavuz Semiz, Ralfi Singer, Ilteris Oguz Topal, et al. A Case of Linear Scleroderma En Coup de Sabre Accompanied with Migraine with Visual Aura and Idiopathic Intracranial Hypertension. Indian J Dermatol. 2023; 68 (3): 346-348. DOI: 10.4103/ijd.ijd_992_22.

7. Glaser D. H., Schutt S. C., Schollaert-Fitchil K., Torok K. Linear Scleroderma of the Head - Updates in management of Parry Romberg Syndrome and En coup de sabre: A rapid scoping review across subspecialties. Eur J Rheumatol. 2020; 7 (Suppl1): S48-S57. DOI: 10.5152/eurjrheum.2019.19183.

8. Papara C., De Luca D. A., Katja Bieber Morphea. The 2023 update Front Med (Lausanne). 2023; 10: 1108623. DOI: 10.3389/fmed.2023.1108623.

9. Zhuo X. W., Fang F., Gong S. Analysis of clinical and imaging features of 6 cases of linear scleroderma en coup de sabre with central nervous system involvement in children Chinese journal of pediatrics 2022; 60 (11): 1147-1152. DOI: 10.3760/cma.j.cn112140-20220429-00396.

10. Winnie Fan, Bianca Obiakor, Rebecca Jacobson, et al. Clinical and therapeutic course in head variants of linear morphea in adults: a retrospective review Arch Dermatol Res. 2023; 315 (5): 1161-1170. DOI: 10.1007/s00403-022-02478-1.

11. Zaid Waqar, Haris Majid. Neurological Manifestations in Two Cases of En Coup De Sabre Case Reports J Coll Physicians Surg Pak. 2022; 32 (12): SS193-SS196. DOI: 10.29271/jcpsp.2022.Supp0.SS193.

12. Lis-Święty A., Brzezińska-Wcisło L., Arasiewicz H. Neurological abnormalities in localized scleroderma of the face and head: a case series study for evaluation of imaging findings and clinical course. Int J Neurosci. 2017; 127 (9): 835-839. DOI: 10.1080/00207454.2016.1244823.

13. Noor Alwash, Naila Dinani, Jessie Felton. A case of multiple cerebral cavernomas associated with en coup de sabre scleroderma 2020; 37 (1): 237-238. DOI: 10.1111/pde.14052. Epub 2019 Nov 2216.

14. Sartori S., Martini G., Calderone M., Patrizi A., Gobbi G., Zulian F. Severe epilepsy preceding by four months the onset of scleroderma en coup de sabre. Case Reports Clin Exp Rheumatol. 2009; 27 (3 Suppl 54): 64-67.

15. Laxer R. M., Zulian F. Localized scleroderma Curr Opin Rheumatol. 2006; 18 (6): 606-613. DOI: 10.1097/01.bor.0000245727.40630.c3.

16. Amaral T. N., Peres F. A., Lapa A. T., et al. Neurologic involvement in scleroderma: a systematic review. Semin Arthritis Rheum. 2013: 43 (3): 335-347. https://doi.org/10.1016/j.semarthrit.2013.05.002.

17. Tollefson M. M., Witman P. M. En coup de sabre morphea and Parry-Romberg syndrome: a retrospective review of 54 patients. J Am Acad Dermatol. 2007; 56 (2): 257-263. DOI: 10.1016/j.jaad.2006.10.959.

18. Knights H., Minas E., Khan F., et al. Magnetic resonance imaging findings in children with Parry-Romberg syndrome and en coup de sabre. Pediatr Rheumatol Online J. 2021; 19 (1): 42. DOI: 10.1186/s12969-021-00512-6.

19. Héron E., Fornés P., Rance A., et al J. N. Brain involvement in scleroderma: two autopsy cases. Stroke. 1998; 29 (3): 719-721.

20. Kraus V., Lawson E. F., von Scheven E., et al. Atypical cases of scleroderma en coup de sabre. J Child Neurol. 2014; 29 (5): 698-703. DOI: 10.1177/0883073813520494.

21. Stone J., Franks A. J., Guthrie J. A., et al. Scleroderma "en coup de sabre": pathological evidence of intracerebral inflammation. J Neurol Neurosurg Psychiatry. 2001; 70: 382-385.

22. Dupont S., Catala M., Hasbound D., et al. Progressive facial hemiatrophy and epilepsy: a common underlying dysgenetic mechanism. Neurology. 1997; 48: 1013-1018.

23. Kanzato N., Matsuzaki T., Komine Y., et al. Localized scleroderma associated with progressing ischemic stroke. J Neurol Sci. 1999; 163 (1): 86-89. DOI: 10.1016/s0022-510x(98)00267-6.

24. Takahashi T., Asano Y., Oka T., et al. Scleroderma en coup de sabre with recurrent episodes of brain hemorrhage. J Dermatol. 2016; 43 (2): 203-206. DOI: 10.1111/1346-8138.13023.

25. Fox C., MD, MAS. Pediatric Ischemic Stroke. Cerebrovascular Disease. 2023; 2 (29): 566-583. DOI: 10.1212/CON.0000000000001239.

26. Guerreiro L., Sofia Rosado Julião, Alves M. Ischemic stroke and homocysteine: To test or not to test? Rev Port Cardiol. 2023; 42 (11): 931-932. DOI: 10.1016/j.repc.2023.04.016.

27. Morales-González V., Galeano-Sánchez D., Covaleda-Vargas J. E., et al. Metabolic fingerprinting of systemic sclerosis: a systematic review. Front Mol Biosci. 2023; 10: 1215039. Published online 2023 Aug 8. DOI: 10.3389/fmolb.2023.1215039.

28. Lemaire R., Burwell T., Hong Sun, et al. Resolution of Skin Fibrosis by Neutralization of the Antifibrinolytic Function of Plasminogen Activator Inhibitor 1 Arthritis Rheumatol. 2016; 68 (2): 473-483. DOI: 10.1002/art.39443.

29. Borodina I., Salavatova G., Shardina L. Polymorphisms of F2 (G20210A), F5 (G1691A), F 7 (G10976A), F 13(G13T), FGB, ITGA2, ITGB3, PAI-I genes and its association with thrombotic complications in patients suffering from Takayasu aortoarteritis of Urals population. Turk Kardiyol Dern Ars. 2021; 49 (6): 448-455. DOI: 10.5543/tkda.2021.69741.

30. Filippini A., Tamagnone L., D'Alessio A., et al. Endothelial Cell Metabolism in Vascular Functions Cancers (Basel). 2022; 14 (8): 1929. DOI: 10.3390/cancers14081929.