Via Research Recognition Day Program VCOM-Carolinas 2025

Case Reports

Neurological and Vascular Complications in Klippel Trenaunay Syndrome: A Case highlighting Epilepsy, Hemiplegic Migraines, and Septicemia management Gabrielle Aluisio 1 , MBA, OMS-III, Lindsey Saleski 1 , DO, MBA 1. Edward Via College of Osteopathic Medicine – Carolinas Campus Introduction Case Discussion

• Klippel-Trenaunay Syndrome (KTS) is a congenital vascular disease that classically is a triad of cutaneous capillaries malformations or port-wine stains, anatomically abnormal varicosities, and limb hypertrophy including soft tissues and/or bones [1-4] • KTS can be diagnosed clinically when at least two components of the classic triad are present [1,3] • KTS has been linked to somatic mutations in the phosphatidylinositol-4-5-bisphosphate 3 kinase catalytic subunit (PIK3CA) gene, which drive cellular overgrowth via the AKT/mTOR pathway [1,5] • The vascular abnormalities are described as a slow-flow combined capillary-lymphatico-venous malformation devoid of arterio-venous fistulas seen in Parkes-Weber Syndrome [2,3,6] • Anomalous superficial veins often develop in the extremity which can cause cellulitis, pain, edema and are at risk for thrombophlebitis [4,6] • A 41-year-old female with a history of KTS, epilepsy, and hemiplegic migraines presented to the emergency department with worsening left lower extremity cellulitis and non-healing ulcers on the left second digit of the foot and lateral lower extremity (figure 1). • She reported progressive ulceration and erythema for two weeks with increased pain and purulence two days prior to arrival to ED. Her presentation upon arrival was accompanied by fever and generalized weakness. Case

• On physical examination, left lower extremity showed a birthmark consistent with a faded port-wine stain, prominent venous and capillary discoloration, and cyst-like venous malformations as shown (figure 2) . • Venous reflux studies confirmed superficial venous insufficiency to the left great saphenous vein. • MRI revealed vascular malformations in the vastus lateralis muscle and inflamed inguinal lymph nodes consistent with infection, as shown in figure 3.

• KTS is part of a spectrum of clinical findings and variations in the severity of vascular malformations can influence prognosis • Clinical findings progress over time with worsening venous insufficiency and continued capillary, venous, and limb overgrowth • Treatment of patients with KTS is optimized with a multi disciplinary team approach with care coordination • Cellulitis due to stasis from venous and lymphatic abnormalities can lead to sepsis without proper skin care. • The use of compression stockings and limb elevation can minimize lymphedema and venous insufficiency • Although the pathogenesis of hemiplegic migraines are not fully understood, abnormal blood vessel development in KTS may lead to an increased incidence of headache • There are limited reports of KTS with associated intracranial AVMs which may lead to symptoms such as seizures, headaches, and progressive numbness, although in this patient intracranial AVMs were not evident.

Figure 2. Left lower extremity

Lab values support a diagnosis of septicemia d/t cellulitis. Lab Value WBC 18.9 x 10 9 /L (x41.50-11 9 /L) Procalc itonin 59.35 ng/mL (<0.1 ng/mL) Tr aetmu rpee 1( 9072-°9F9 ° F )

A.

B.

Conclusions

Figure 3 (A & B). MRI of left lower extremity. Red arrows mark vascular malformations measuring 3x5x8 cm

This case demonstrates the complexities of managing acute and chronic complications in Klippel-Trenaunay Syndrome. The interplay of recurrent infections, vascular malformations, and chronic venous insufficiency underscores the importance of interdisciplinary care. Timely intervention and tailored management strategies can mitigate complications and improve patient outcomes.

• Patient was treated with IV vancomycin and wound care. • Patient continues to follow up weekly with wound care and is using pressure bandages, silver nitrate for chemical cautery, 1% hydrocortisone and 1% chloramphenicol compound cream for hypergranulation as well as compression stockings (figure 4).

References

[1] Naganathan S, Tadi P. Klippel-Trenaunay-Weber Syndrome. [Updated 2023 Apr 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558989/# [2] Harnarayan, P., & Harnanan, D. (2022). The Klippel-Trénaunay Syndrome in 2022: Unravelling Its Genetic and Molecular Profile and Its Link to the Limb Overgrowth Syndromes. Vascular health and risk management , 18 , 201 – 209. https://doi.org/10.2147/VHRM.S358849 [3] Sung, H. M., Chung, H. Y., Lee, S. J., Lee, J. M., Huh, S., Lee, J. W., Choi, K. Y., Yang, J. D., & Cho, B. C. (2015). Clinical experience of the Klippel-Trenaunay syndrome. Archives of Plastic Surgery , 42 (05), 552 – 558. https://doi.org/10.5999/aps.2015.42.5.552 [4] Asghar, F., Aqeel, R., Farooque, U., Haq, A., & Taimur, M. (2020). Presentation and Management of Klippel-Trenaunay Syndrome: A Review of Available Data. Cureus , 12 (5), e8023. https://doi.org/10.7759/cureus.8023 [5] Vahidnezhad, H., Youssefian, L., & Uitto, J. (2016). Klippel-Trenaunay syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS). Experimental dermatology , 25 (1), 17 – 19. https://doi.org/10.1111/exd.12826 [6] Sidawy, A. N., Perler, B. A., & Rutherford, R. B. (2023). Rutherford’s vascular surgery and endovascular therapy . Elsevier.

Figure 4. Left lower extremity ulceration A) upon arrival and B) 4 months follow-up A. B.

Figure 1. Left lower extremity cellulitis and ulceration

2025 Research Recognition Day

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