Three cases of stroke following peripheral venous interventions

Published online before print 21 March 2011, doi: 10.1258/phleb.2010.010044
Phlebology October 2011 vol. 26 no. 7 280-284
Three cases of stroke following peripheral
venous interventions

Author Affiliations Correspondence: Dr Kurosh Parsi FACD FACP
, Suite 1501, 520 Oxford St, Bondi Junction, NSW 2010, Australia. Email:

We report three cases of stroke in association with peripheral venous interventionsthat each included foam ultrasound-guided sclerotherapy (UGS). All three femalepatients experienced a right middle cerebral artery (MCA) stroke causing dysphasiaand left hemiparesis. A patent foramen ovale was found in each patient. The firstincident occurred two days after foam UGS to treat small tributaries of a greatsaphenous vein (GSV). Paradoxical clot embolism was presumed in this case whereconcurrent deep vein thrombosis with non-occlusive thrombus in a medialgastrocnemius vein extending to the popliteal vein was detected on ultrasound. Thesecond case occurred immediately at the completion of foam UGS and ambulatoryphlebectomy to treat GSV tributaries. Paradoxical gas embolism was demonstrated inthis patient confirmed by visualization of bubbles in the right MCA on CT angiography.
The third case occurred one day after endovenous laser ablation (1470 nm) and foamUGS to treat both great and small saphenous veins. No specific cause could beconfirmed in this patient. Sodium tetradecyl sulphate foam was used in all three cases(3%, 16 mL; 1.5%, 4 mL and 3%, 25 mL, respectively). All three patients recoveredcompletely within a few days.
The present report describes cerebrovascular events (CVEs) following peripheralvenous interventions in three female patients with patent foramen ovale (PFO). Thefirst patient was treated with foam ultrasound-guided sclerotherapy (UGS) alone whilethe other two underwent concurrent ambulatory phlebectomy (AP) and endovenouslaser ablation, respectively. Sodium tetradecyl sulphate (STS, supplied as FIBRO-VEIN 3%, Australian Medical and Scientific, Chatswood, NSW, Australia) was used inall three cases.
Case reports
Patient 1: probable clot embolism
A 56-year-old female presented with recurrent varicose veins. External stenting ofsaphenofemoral junctions (SFJs) using Venocuff ® and multiple avulsions were performed 15 years before. There was a history of migraines since the age of 12 butno personal or family history of venous thromboembolism (VTE), thrombophilia orCVE. She took tibolone, atorvastatin, omeprazole and calcium supplements. Onexamination, there were prominent varicosities in medial calves (C2). Duplexultrasound (DUS) showed bilateral great saphenous vein (GSV) and left smallsaphenous vein (SSV) incompetence.
In February 2006, her left GSV, SSV and intersaphenous veins were treated with UGS(STS 3% foam, 15 mL) followed by a 40 mg subcutaneous injection (SCI) ofenoxaparin. Foam was prepared with modifications to the original Tessari methodusing STS 3% in a liquid-to-air ratio of 1:3 (1 in 4). Seven days later, she received 5mL of STS 3% foam in a second UGS session. On one-week follow-up, she wasasymptomatic-but DUS detected occluded segments of the left femoral (FV, 13 cm)and medial gastrocnemius veins (MGV, 9 cm), both associated with sclerosedperforators. Enoxaparin was administered for three weeks. Sequential DUS studiesshowed complete recanalization of the MGV but the FV remained occluded (11 cm)one year later.
In March 2006, her proximal GSV was treated with endovenous laser ablation (EVLA)(810 nm). This was followed by three sessions of UGS (STS 3% foam, 3, 3 and 6 mLper session) for the remaining segments with no complications. On six-week follow-up, DUS showed a lumen in the GSV and residual calf and thigh tributaries.
In November 2006, the residual veins of the right leg and small tributaries of the leftpopliteal fossa were treated with UGS (STS 3% foam, 16 mL) covered by enoxaparin40 mg SCI. Full-length Class II graduated compression stockings (GCS II) wereapplied and she was instructed to walk for 30 minutes following the procedure. Twodays later, she had a right middle cerebral artery (MCA) stroke causing dysphasia andleft limb and facial paralysis but no visual disturbances. Magnetic resonance imaging(MRI) on the same day revealed ischaemic changes within the right lentiform nucleusand an incidental finding of a pituitary adenoma but no air bubbles were demonstrated.
She made a complete recovery within one hour of the onset of symptoms. DUSshowed normal carotid and vertebral arteries but there was non-occlusive thrombus inthe right MGV extending to the popliteal vein. A trans-oesophageal echocardiogram(TOE) revealed a PFO measuring 25 mm. Detailed thrombophilia screening wasnegative. The patient was commenced on aspirin, enoxaparin and warfarin. Threeweeks later and while on anticoagulants, she experienced transient left-sidednumbness but no infarct or haemorrhage was detected on MRI. The PFO was closedpercutaneously a week later. On one-year follow-up, she did not report any furtherneurological or thrombotic events.
Patient 2: Gas embolism
A 59-year-old female presented with right lower limb varicose veins. She had a historyof classic migraines (with aura), for which she took ibuprofen intermittently. At the ageof 39, she had suffered a stroke which presented with a left facial hemiparesis. Shewas treated with aspirin 100 mg daily, which was ceased three years following theevent. She had no personal or family history of VTE or thrombophilia. Her currentmedications included atorvastatin 40 mg daily and fish oil supplements. Onexamination, she had prominent varicosities in the right posterior calf region, oedemaand lipodermatosclerosis affecting the right medial ankle (C4b). DUS showed a rightGSV incompetence, which was treated uneventfully with EVLA (810 nm) in March2010.
Four weeks later, she underwent foam UGS (STS 1.5%, 4 mL) for the right distal GSVand posterior arch vein (PAV). This was followed by AP performed in the left lateraldecubitus position, for the remaining calf varicosities. At the completion of AP, thepatient was turned into the supine position and asked to lift her leg for application ofGCS. Within seconds of lifting the leg, she became unresponsive and exhibited analtered mental state with slurring of speech, disorientation, a dense left arm and leghemiplegia, and an extensor plantar response. She was transferred to hospital within20 minutes where a computerized tomography (CT) angiogram of the brain revealed aright MCA air embolus (Figure Two hours later, she was treated with tissueplasminogen activator (t-PA). Within several minutes of this treatment, her mentalstatus returned to normal and there was a dramatic improvement in her neurologicalstate abated with only a slight left facial droop and left-sided weakness (9/10 strength).
Repeat CT several hours later confirmed complete resolution of the right MCA airembolus and no abnormalities of the right cerebral cortex. MRI the following dayrevealed small micro-infarcts of the right basal ganglia. She was monitored in hospitalfor three days and placed on clopidogrel 75 mg daily. TOE revealed a small PFO. Thepatient's residual facial and lower limb weakness fully resolved by discharge. DUSshowed normal carotid arteries, occlusion of both GSV and PAV but no deep veinthrombosis (DVT). At three-month follow-up, she reported no further neurological orthrombotic events.
Patient 2: (a) Axial post-contrastcomputerized tomography (CT) ofbrain obtained within one hour ofthe onset of symptoms showing anair embolus in the right middlecerebral artery (MCA). (b) Alteredperfusion on post-contrast CTperfusion imaging showingdecreased flow in the right MCA View larger version: Patient 3: debatable cause
A 64-year-old female presented with bilateral skin signs of chronic venoushypertension. There was no personal or family history of migraines, VTE,thrombophilia or CVE. She took pentoxifylline 400 mg twice daily and aspirin 80 mgtwice a week for prevention of travel-related thrombosis and thyroxine for hypothyroidism. On examination, she had prominent varicosities in medial calves,bilateral oedema and dermatitis, and lipodermatosclerosis affecting the left medialankle (C4b). DUS showed bilateral incompetence of GSV and SSV.
In February 2008, her left GSV and SSV were treated with EVLA (810 nm) followed bytwo sessions of UGS (STS 1.5% foam, 15 mL per session) for the remainingsegments with no complications. Foam was prepared using STS 1.5% in a 1:4 (1 in 5)ratio.
In July 2008, her right leg was treated with a combination of EVLA and UGS. One hourprior to the procedure, 30 g of lignocaine/prilocaine 5% (EMLA) cream was appliedunder occlusion along the length of both GSV and SSV and enoxaparin 40 mg SCIwas administered. Proximal GSV was catheterized and the laser probe was placed 2cm distal to the SFJ. A volume of 100 mL of tumescent anaesthesia (20 mL ofxylocaine 1% with adrenalin 1 in 80,000, 7 mL sodium bicarbonate in normal saline)was infused into the peri-venous space. The thigh segment of the GSV was treatedwith a 1470 nm laser (Biolitec, Jena, Germany) at 14 W, continuous wave (CW), 63.5J/cm linear endovenous energy density and 2.6 mm/second withdrawal rate. Theproximal 2/3 of SSV was treated with EVLA (12 W, CW, 80 J/cm, 1.5 mm/second, 76mL tumescent) and the remaining segments were treated with UGS (STS 1.5%, 25mL). GCS II and two layers of short stretch bandages were applied. She wasinstructed to walk for 30 minutes.
Our patient felt unwell during that evening and was taken to the hospital following a fallthe next morning. She was diagnosed with a right MCA stroke presenting withdysphasia and left limb and facial paralysis. A CT scan of the brain was normal butMRI performed several days later confirmed an infarct within the right frontal andtemporo-parietal lobes. Neither modality demonstrated air bubbles in the cerebralcirculation. TOE revealed a PFO measuring 18 mm. DUS showed a small plaqueinvolving the left carotid bulb, occlusion of both GSV and SSV but no DVT. She madea full neurological recovery after four days. The PFO was closed percutaneously threeweeks later and she was commenced on perindopril and atorvastatin. On two-yearfollow-up, she reported no further neurological or thrombotic events.
The overall incidence of neurological complications of sclerotherapy is suggested tobe less than 2%.From 4059 foam UGS procedures performed in our Sydneypractice during a six-year period, we have two known occurrences of stroke, giving anapproximate annual incidence of 0.01%. A literature search revealed nine publishedcases of stroke following sclerotherapy since These included four cases ofstroke complicating and five following foam Furthermore,four cases of transient ischaemic attacks (TIA) have been reported after foam We postulate that the stroke in our first patient was most likely due to paradoxical clotembolism (PCE). This event had a delayed onset of two days after the treatment witha concurrent finding of DVT involving the right MGV and the popliteal vein. This patienthad developed a left FV occlusion following a previous sclerotherapy treatment. Apituitary adenoma was found on MRI. Intracranial tumours, including pituitaryadenomas, are associated with an increased risk of In such patients, VTE riskfactors including genetic thrombophilias and the presence of a right-to-left shunt playan important role in the pathogenesis of Small embolic clots, which wouldnormally be lodged and lysed in the lungs without overt clinical sequelae, canparadoxically embolize to the brain causing a Microemboli can also causetransient neurological with recovery when the emboli have lysed and In two cases described here, stroke occurred despite the prophylactic single dose ofenoxaparin. The second patient was also on antiplatelet agents (aspirin andpentoxifylline). A recent study has shown that the single dose of enoxaparin isineffective in prevention of DVT We have since ceased this practice as aprophylactic measure.
We postulate that paradoxical gas embolism (PGE) was responsible for stroke in oursecond patient. This is based on the immediate onset of symptoms after the procedureand visualization of gas emboli on CT angiography obtained within the hour of theonset of symptoms. Bubbles have been visualized to enter the right heart within oneminute of foam sclerotherapy despite all treatment Five publishedcases including three cases of and two cases of had an immediateonset following foam sclerotherapy. In this group, gas emboli were visualized in thecerebral circulation of two stroke and the neck arteries of one andone TIA Similarly, cases of stroke and cerebral ischaemia following theechocardiogram Bubble Studies (injection of saline froth) are all reported to occur The cause of stroke in our third patient can be debated. The total volume of thesclerosant foam injected (25 mL) exceeded the volumes recommended by theEuropean consensus (<10 This large volume may raise the possibility of PGE.
No gas emboli were visualized on MRI but imaging for gas emboli can be negative asair and CO 2 are absorbed We have subsequently limited the volume of the injected foam to 15 mL (<20 mL) per session to comply with the Australasian Collegeof Phlebology Standards.
This patient underwent concurrent EVLA. Tongues of thrombus have been observedfollowing EVLA of the GSV extending into the common femoral Furthermore, there has been a recent case report describing stroke following EVLA.We used a 1470 nm laser with a relatively high power setting (12–14 W) comparedwith those currently recommended by the manufacturer (5–7 W). It is unknownwhether the higher laser power can result in formation of loose clots with potential forembolism. DUS follow-up showed good occlusion of the GSV and no associatedtongue of thrombus or concurrent DVT. These negative findings, however, do not ruleout PCE from the segments treated with laser or sclerosants. Furthermore, EVLA alsogenerates steam bubbles visualized on DUS generating a ‘ring down' artefact. Thesebubbles have been observed to enter the cardiac chambers soon after EVLA (Dr NickMorrison, personal communication via email to K Parsi, on27 July 2010). It is to be shown whether such bubbles can act as a source for PGE.
In summary, we report three cases of stroke in association with peripheral venousinterventions that each included foam sclerotherapy. All three patients recoveredcompletely and had no residual neurological deficit. The common risk factor was thepresence of a PFO.
We are grateful to Dr Chris Holden, radiologist with Imaging Independently, forproviding the CT angiography images and Dr Nick Morrison for personalcommunication.
Accepted October 14, 2010.
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