Transient neurologic event following administration of foam sclerotherapy

Case

A 56-year-old man presented for the cosmetic treatment of reticular veins and spider veins primarily in the posterior of both thighs. The patient, a physician, had been treated with sclerotherapy before at another clinic on more than one occasion with good results; the type and form (liquid or foam) of sclerotherapy he received in the past were unknown.

The patient denied history of migraine headaches or other medical history on his intake form. He never smoked cigarettes, exercised regularly, and maintained a normal weight. The patient was treated with 8 cc foamed 0.5% polidocanol (Asclera, Merz Pharmaceuticals). The foam was prepared with a 1:4 ratio of liquid to room air using the Tessari technique involving at least 20 passes of agitation through a three-way stopcock using 10 cc syringes (McKesson). Two aliquots of 4 cc foam were generated using the same syringes twice for a total of approximately 8 cc foam. Foam was injected into visible reticular veins measuring between 1 and 3 mm using direct visualization immediately after foam preparation. Foam was re-agitated between injections in order to maintain consistency and no boluses of air were observed. The span of time between agitation or repeat agitation of foam and administration of each injection was brief, less than 10 s by the author’s estimation. The author estimates approximately three to four injections were performed on the left leg and two on the right leg. No ultrasound-guided injections were performed. The injections were performed with the patient in a slight (∼10°) Trendelenburg position with approximately 70% of the foam injected in the left posterior thigh and the balance divided between the right posterior leg and medial right lower leg. While bandages comprising gauze, tape, and 20–30 mmHg compression stockings were being placed, approximately 10 min after the injections were completed, the patient reported feeling lightheaded. He was maintained in Trendelenburg and given fruit juice to drink with a straw. After 2–5 min, the patient reported weakness of the left upper and lower extremities. An initial neurologic examination with the patient still in Trendelenburg position revealed left-sided hemiplegia with 2/5 muscle strength in left upper, lower extremities and normal, 5/5 muscle strength in right upper, lower extremities. Strength was assessed in the biceps, triceps, wrist flexors and extensors, grip, hip flexors, and ankle dorsal flexion and plantar flexion. His National Institute of Health Stroke Scale (NIHSS) was 6 out of 42 making this a moderate stroke presentation. The patient was placed into steep Trendelenburg (∼30°) and oxygen was administered by nasal cannula. Blood pressure was 128/75, heart rate was 77, and heart rhythm was normal sinus rhythm on a portable monitor. Bedside blood glucose measurement was normal.

Emergency medical services (EMS) was summoned and arrived approximately 5 min later at which point the patient had improved to 4/5 in strength testing. The patient was observed an additional 20 min over which his strength returned completely to normal. No speech, cognitive, or visual disturbances were ever observed. No headache, chest pain, or shortness of breath were ever reported. The patient declined transfer to the hospital for further evaluation, remaining under observation in the office for approximately 3 h during which time he remained completely asymptomatic. The patient declined a follow-up echocardiogram bubble study to evaluate for paradoxical right to left cardiac shunt due to the risk of repeated transient ischemic attack (TIA) or stroke. The patient has not experienced any neurologic symptoms in the year since this event.

Discussion

PCP foam sclerotherapy is a commonly used practical technique for the treatment of superficial venous disease. Though generally regarded as safe, acknowledged serious complications of foam sclerotherapy include anaphylactic reactions, severe neurologic events including cerebrovascular accident (CVA) and TIA, superificial venous thrombosis, tissue necrosis, edema, and nerve damage.^1,2 Recent meta-analysis of the frequency of serious neurologic events in patients receiving foam sclerotherapy has reported rates as high as 0.9% with 12 radiologically confirmed CVAs and 9 reported TIAs. Many, though not all, of these patients were demonstrated to have a PFO. ³ The authors are aware of four additional unpublished CVAs in patients receiving foam sclerotherapy, including patients with and without documented PFO. Controversy exists whether these neurological events are always a function of gas embolism with some authors promoting the theory that endothelin may be the cause of these adverse events, despite images showing air bubbles in the middle cerebral artery in at least two cases. ⁴ Even these authors advocate for the use of physiologic gases including O² and CO ² for foam sclerotherapy, citing the ability to safely administer larger volumes of foam and the lack of any recorded CVAs in prior studies using O² and CO², though one case of TIA has been reported after the injection of 10 cc of foam prepared with O². ⁵ Current guidelines call for administration of no more than 10 cc of foam and recommend room air (Level 1A recommendation) or a mixture of carbon dioxide and oxygen (Level 2B recommendation).^6–8 Some authors have called for physiologic gas preparation or volume limits in patients with known PFO or history of migraine despite the fact there have been events in patients treated with room air, physiologic gas, small amounts of foam, and no detectable patent foramen ovale (PFO), atrial septal defect (ASD), or history of migraine.

In this case study, we report a healthy man who experienced a transient neurologic event consistent with a TIA after reticular administration of less than 10 cc of a room air 0.5% polidocanol foam sclerotherapy preparation. Though this patient’s symptoms resolved within several minutes, it is not clear which patients would be more likely to progress to a complete CVA in similar circumstances. Studies comparing room air and physiologic gas foam sclerotherapy preparations found no difference in treatment efficacy. ⁹ Given the high estimated prevalence of PFO and ASD, 1 in 4 ¹⁰ in the USA, and the question of whether endothelin or air embolism (or potentially both) causes severe neurologic events in patients treated with foam sclerotherapy, current guidelines recommending physiologic gas and immediate administration seem reasonable but potentially impossible to implement on a wide scale basis. The Tessari technique, though useful, is inherently imprecise in creating a standardized bubble mixture size in the laboratory, let alone the real world where clinicians may vary angles in a three way stopcock, the ratio of gas to liquid and timing to administration pending intravenous access. The Double Syringe System (DSS) technique, which eliminates the third channel and reduces variability in the angle of the stopcock, may further improve consistency. ¹¹

The role of compounded versus branded preparations of polidocanol and sotradecol and their potential role in central nervous system effects has not been elucidated. Polidocanol endovenous microfoam (PEM, BTG, London, UK) is a commercially available preparation which combines physiologic gas with 0.5% and 1.0% polidocanol in a consistent, predictable fashion. In studies reported to date, no severe cerebrovascular events or migraine headaches have been reported. ¹² Currently, approved for the treatment of visible varicosities and saphenous vein insufficiency, use in the USA is currently limited due to non-uniform reimbursement policies.

Continued investigation into the potential role of product, gas, volume, and technique to identify optimal approaches and products may further refine the consistency and safety of foam sclerotherapy.