In the Thick of It

Diagnosis and Treatment for Venous Form of Thoracic Outlet Syndrome with Comorbid Tick-Borne Infections

By Julia Greenspan, ND

Thoracic outlet syndrome is surprisingly difficult for patients to receive a diagnosis even when presenting with clear, objective findings. Most patients do not have the time to wait to see a specialist and end up in the emergency room with symptoms of arm swelling, chest pain, and elevated blood pressure that can feel like a cardiovascular event. Patients can present with normal EKG, ultrasound, and troponin levels, so most are sent home and told they are fine. Hopefully, this article will help in the more rapid diagnosis, give proper referrals, and start patients on anticoagulant medications as soon as possible. 

Introduction

Thoracic outlet syndrome (TOS) is caused by the narrowing of the thoracic outlet, which causes brachial plexus compression and blood vessels supplying the axilla and upper extremities. There are three different types: neurogenic nTOS, which makes up 90% of cases; vascular forms, arterial aTOS; and venous vTOS, between 5-10%, which are rarer but more dangerous when they do present.¹ Literature was found to report conflicting data on gender, with some stating that it is more common in men and others in women. It is most seen with first rib impingement, preceding trauma event, or hypertrophy of the scalene/other muscle of the shoulder with repetitive movements like weightlifting. TOS happens with impingement in three areas: scalene triangle, subcoracoid tunnel (Pectoralis minor area), and costoclavicular gap. In this same area are sympathetic nerve roots and lymphatics. Tumors impacting the thymus and the thyroid can also put more pressure, causing impingement. 

Types of Thoracic Outlet Syndrome

Paget-Schroder Syndrome (PSS), or “effort thrombosis,” has both compression and thrombosis in the subclavian vein. It is a form of vTOS. PSS is rare, 1-4 % of all thrombosis cases annually, and happens in 1-2 people per 100,000. Repeated chronic compression can create scarring and inflammation of the subclavian vein. Then, overburdening the muscle with excess activity can cause immediate injury even though the subclavian vein injury started long before the acute event. The upper chest can have pain, engorged superficial blood vessels, cyanotic presentation, and onset can be due to the event of excessive activity as the trigger.² This is reflected in the case study presented in this article. 

Paget-Schroder Syndrome (PSS)

There are standard physical exams to elicit symptoms and confirm diagnosis further; however, most are used to verify the neurogenic form of TOS. The Adson Maneuver is when the radial pulse is taken with the head extended and then the chin brought to the shoulder of the same side; a decrease in the pulse is a positive outcome. In the Roos Stress Test, the patient raises both arms to the top of his head, shoulders at 90° abduction with outward rotation, and elbows in 90° flexion. They then opened their hands for 3 minutes.  A positive outcome with this test can elicit symptoms in 95% of cases of TOS.³ Imaging like ultrasound or duplex imaging with ultrasound combined with Doppler, x-ray to identify cervical rib, and CT angiogram with contrast to identify reduced blood flow due to blockage are commonly used. A D-Dimer test is a non-invasive, easy method combined with ultrasound or other imaging to confirm the presence of upper extremity DVT.⁴ 

Case Presentation

Patient History

A 49-year-old postmenopausal female taking bioidentical hormone therapy develops pain in the left axilla and down her left arm during a typical morning workout incorporating weight lifting of the upper body. The pain came on quickly after her arms outstretched during the child’s pose midway through the workout. She is a non-smoker and exercises regularly but has a more sedentary job involving much typing. She is a business owner, medical practitioner, and single mother of two. Three days prior, she had deep tissue massage in both the axilla and around the clavicular area to release tension in the shoulder. 

She weighed 150 pounds and was 5’6”. She has a history of Hashimoto’s thyroiditis controlled with porcine-derived thyroid hormone. She is on a 200mg progesterone capsule at bedtime and an estradiol patch of 0.05mg, which is changed twice weekly. She occasionally takes supplements for general health and has no other significant health issues. 

 Initial Symptoms and Diagnosis

When the pain started, she thought it might be a cramp in the deltoid or bicep. She continued with her workout but noticed that about 30 minutes later, in the shower, the arm was swollen in the bicep, and there was increased erythema and pronounced veins in the hand. She decided to go to the ER due to concerns about developing a blood clot. Her vitals were normal. Adson’s maneuver was negative, complete blood cell count/metabolic panel negative, ultrasound negative, troponin I HS was at 33 ng/L (>=120ng/L), and two hours later, it was at 4 ng/L (<=33 ng/L). 

The standard measurement of what is considered abnormal troponin I HS levels is specific, with different values associated with gender. With initial testing, women and men have the same reference range and become more gender-specific with 2-hour follow-up measurements.  Women have a lower reference range than men due to age and hormone-related differences regarding higher estrogen levels in cycling females. The patient was on hormone replacement therapy at the time of the test; both estrogen and progesterone. With troponin I HS levels, there is more of a concern for myocardial infarction in women, with the rate of change from the initial value with lower reference range values triggering a concern then compared to men. For women, any initial testing between 9-34 ng/L with an increase in value 2 hours later greater than or equal to 7 ng/L is a concern for a myocardial event. The patient was told that her numbers were standard and that it was not a concern for a cardiac event. She was sent home with recommendations to take NSAIDS for sprain/strain and to return if the symptoms worsen. 

Hospital Visits and Diagnostic Challenges

Over the next week, the arm increased in size based on position and temperature. There was also discoloration between bright red and purple. Chest pain intensified with more pronounced veins in the left pectoral region. She was having episodes of stuttering, tongue-tingling, the enunciation of words, and dysphagia. She returned to the ER. The ER staff focused more on imaging and serology without conducting a thorough physical exam of the left arm to visualize the pronounced veins, swelling, and discoloration. The focus was more on ruling out MI, pulmonary embolism, or DVT with imaging plus serology. Troponin levels at 44 ng/L are now considered elevated, and 38 ng/L are still elevated two hours later, remaining at that level with a third specimen six hours later. Ultrasound was performed, and a CT scan with/without contrast of the left arm outstretched above the head was normal. A D-dimer was not performed. The hospital said either imaging was done or D-dimer, but not both. 

The chest pain continued to increase, and blood pressure, normally 110/65mmHG, was now 169/95mmHG. After consulting with medical staff, they agreed to keep her overnight and did a stress ECHO the following day, which was normal. Continuous heart monitoring was regular throughout the stay. Blood pressure was variable with constant monitoring that remained elevated more than typical for patients. The pain was managed with morphine and anxiety with the intravenous push of lorazepam 1mg. The patient was sent home the next day with advice to meet with an orthopedic specialist and that anxiety might be the cause. No physical exam was done throughout the visit, and she only saw a doctor twice for a brief conversation. 

Diagnosis and Diagnostic Tests

Physical Examinations

The following week, she met with an orthopedic specialist who said it was not thoracic outlet syndrome after a physical exam and wrote orders for an MRI of the left shoulder. Soon after that, she met with a vascular specialist, where Thoracic Outlet Syndrome venous form or Paget-Schroder Syndrome was confirmed based on a clinical history of onset of symptoms, pronounced veins in the left pectoral region, erythema, swelling, and positive Roos stress test, which elicited chest pain when arms were brought down into lap. Roos stress test was without symptoms while arms were raised. This was reported to the doctor, who sent her for stat D-Dimer after the visit, which was 1.98 mg/L (0.19-0.52 mg/L). The plan was to start anticoagulation after the D-dimer was completed and have surgery within the upcoming week for left rib resection.  

Treatment and Management

Medical Treatment 

On the way home from a visit with the vascular surgeon, symptoms started to worsen with pressure behind the left eye, difficulty with speech, and chest pain, making it hard to breathe. She was told to return to the ER, and the vascular team would meet her there. Compression from the blood pressure cuff by the nursing staff during the initial screening elicited more symptoms and could not be completed. CT with contrast showed reduced blood flow through the subclavian-axillary vein. Tropinin was at 57 ng/L  and went to 54 ng/L two hours later. 

She was started on a heparin drip, morphine for pain, and Ativan for anxiety. Nothing by mouth (NPO) orders started for surgery the following morning for venoplasty to remove the clot. After the procedure, the surgeon noted scar tissue with webbing in the subclavian vein, which was an older injury. The patient did have a history of a PICC line placed for over five months in the left arm with the treatment of a tick-borne infection, Lyme disease, and Babesia duncani thirteen years prior. The patient opted to have the left first rib resection the next day with a second surgery to reduce recovery time. The patient was kept overnight and sent home after the second surgery. The patient started on Apixaban 5mg twice per day for 90 days. There was a complication of allergic reaction with allergic urticaria from the presurgical cleanser requiring a five-day steroid tapper. She continued to recover; however, her arm remained swollen. This was thought to be due to surgical recovery. 

Follow-Up and Further Diagnostic Challenges

She continued to recover but had difficulty multitasking, typing, and tracking with her eyes on the screen, which made her feel woozy. Therefore, she used dictation software to complete tasks. If this had not been available, she would not have been able to return to work. 

Thirty days later, she had an ultrasound performed with a vascular specialist, showing chronic changes consistent with prior DVT but otherwise normal. The next day, while at work, she developed chest pain, dizziness with crossing her legs, and discoloration of the arm with a purple tinge. She went back to the ER. D-Dimer was still at 1.96 mg/L on Apixaban. EKG and chest x-ray normal. Troponin was 37 ng/L, considered high, and remained at 36 ng/L two hours later. PT and INR were normal. The metabolic panel showed ALT at 60 U/L and AST at 40 U/L. CT scan with contrast showed a clot formed in the subclavian-axillary junction. The patient started back on intravenous heparin, and repeat venoplasty was completed with a stent placed in the subclavian vein with partial sedation. She went home the same day as a procedure with the anticoagulant changed to Enoxaparin injections twice per day in the abdomen.  

The following day, after the stent was placed, she awoke to a tachycardia event with a heart rate at 150, persisting with chest pain, and called an ambulance. EKG noted abnormality compared to past EKG but was non-specific about changes. Complete blood cell counts and metabolic panel are normal, with troponin at 35 remaining at this same level two hours later. She consulted with her vascular surgeon while in the ER, who also prescribed omeprazole to help with chest pain in case it was GERD-related. Her vascular surgeon also referred her for an urgent appointment with a cardiologist within a few days of discharge from the ER. She met with a cardiologist who cleared her of any cardiac abnormalities, but she continued to have chest pain that would come and go throughout the day. A Holter monitor was ordered for further study. The arm reduced in size with stent placement. 

Anxiety developed, which was not typical for her and was thought to be due to mental and emotional trauma from the events, and she was given lorazepam 0.5mg to take as needed for short-term use to help with sleep. She reported feeling like she was plugged into an outlet, feeling revved up, and having catastrophizing thoughts related to her potentially having another clot or perishing from a heart attack. She began EMDR therapy as well as attending regular sessions for sound therapy healing. She used red light therapy at home daily over her abdomen, chest, and shoulder, which helped improve her parasympathetic tone, but she still struggled with anxiety. 

In the coming days, she continued to have intermittent chest pain, thought to be part of the healing process, stress, or reactions to medications. She returned to the ER but could not get an appointment with her PCP or specialist. The ER doctor suspected esophageal spasms as the patient experienced pain relief with lidocaine, and Maalox alleviated the chest pain. Another CT angiography was performed due to the concerning symptoms and most recent DVT history, which was normal. This was the fourth CT angiography with contrast in six weeks. The outcome was a massive relief for the patient who made an appointment with a gastroenterologist but could not be seen for three months. 

A few days later, the patient opened her patient portal from the hospital and saw the most recent EKG from the ER visit showed a septal infarct, but this was not reported until after the patient was released. There was no call from the ER or a cardiologist about the results. The patient saw this listed on her patient portal days later, and her cardiologist felt this was an inaccurate EKG read compared to past readings. A moment like this increased her anxiety, which was very traumatizing to stumble upon. She went home and continued to have symptoms that were perplexing to all practitioners involved. 

A week later, she went on vacation with family, where she hiked in northern New Hampshire. She was feeling better and more hopeful the worst was over. However, within a week, she returned to the ER due to chest pain intensifying and was not able to get in with any of her practitioners. Chest pain was disturbing sleep and impaired her ability to work. She was waking up two hours after falling asleep with spasms in the left side of her neck, triggering tachycardia with polyuria episodes leading to dehydration, increased bowel motility, urethral spasms, numbness in the groin, nausea without vomiting, numbness down the left leg, periumbilical pain, increased anxiety, panic attacks, abdominal pain on the right and left flank with spams, brain fog, discoloration of the feet with red to purple in the toes, weight loss with muscle wasting of over 10 lbs in three weeks due to decreased appetite and sedentary behavior. She also had shortness of breath along with symptoms of POTS. This was sudden with someone who could do hour-long HITT workouts just a few weeks prior. She continued to use lorazepam 0.5mg as needed for anxiety and 10mg propranolol as needed. 

The symptoms continued and got to the point of being unbearable within the next 10-12 days. She went to the ER once again, where she was kept in the “clinical decision ward” for two days with a work-up due to the lack of a clear diagnosis since these symptoms were not typical post-rib resection and DVT that was resolved according to all diagnostics. All the labs done before were normal, including a CT scan of the chest with contrast, troponin levels, CBC, and metabolic panels. Urinalysis was normal. 

Due to the rapid onset of neurological symptoms in various areas of the body, an MRI of the head was ordered with and without contrast. Tick-borne infections were brought up, but the staff was made aware that the patient had independent labs sent out that were waiting for results, so they did not order labs specific to those conditions. MRI of the brain showed T4/FLAR without active lesions. Due to this being present, an MRI of the cervical and thoracic were done the next day to rule out multiple sclerosis. They were negative for any lesions. In the meantime, abdominal spasms continued, tachycardia throughout the night, and changes in bladder sensations with delayed release of urine. She was released with a diagnosis of abdominal spasms and prescribed cyclobenzaprine 10 mg three times per day.  She only took these medications as needed due to the sedating effects. She met with a neurologist who also ruled out any neurodegenerative disease. 

Serology was also positive for Epstein Barr virus and anticardiolipin IgM antibodies. Urine catecholamines and metanephrine levels were also normal, ruling out pheochromocytoma. She also did a provoked heavy metals test with intravenous ETDA 1.5gms with recent exposure to gadolinium, where her levels were at 110 (reference range <0.8). 

Labs did return for Tick-borne infections, showing bands 23 and 34 IgM present for Borrelia burgdorferi and IgM-positive antibodies for Babesia microti.  She also found a deeply embedded dead tick in the umbilicus that was suspected to have been there for three weeks due to the location of symptoms with umbilical pain and the timing of her vacation in northern New Hampshire.  She was inside most of the summer while this took place and has no other exposure risk with only pets indoors. EDTA was discontinued until treatment for infection was complete. Her G6PD was within normal limits. 

She was started on Atovaquone 10 ml twice per day and Arakoda 100mg 2 tabs for three initial days. Two tabs once per week, valacyclovir 1000mg twice per day, methylene blue 20mg twice per day, low dose naltrexone 1.5mg per day, apixaban 5mg twice per day, doxycycline 100mg twice per day, high potency probiotics two capsules twice per day, liposomal glutathione 1000mg daily, Thyroid replacement 120mg in the morning, L-citrulline 3 grams per day, Quercetin 200mg per day, and grapeseed extract 200mg per day. 

After the first 2-3 days, symptoms of the neuropathies and body pain improved. Anxiety reduced, brain fog improved, and she completed 6 weeks of treatment. Most symptoms were resolved except intermittent chest pain that would arise when working. Over time, the EMDR addressed the post-traumatic stress of the events that contributed to continued chest pain induced by stress; this is now resolved. She also incorporated sound bowl healing, PEMF therapy, acupuncture, massage therapy, Biomagnetic Pair Therapy, EES quantum healing sessions, and supplements. Her current treatment includes Apixaban 2.5 mg twice per day, Vitamin C 2000 mg daily, L-Citruline 3 grams per day, baby aspirin 81mg daily, daily mineral complex one cap per day, D-ribose 5 grams per day, L-Carnitine 500mg per day, Fractionated Marine Lipid Concentrate 1 gram per day, Methylated B12/Folate 1 cap per day, Micronized Diosmin and Hesperidin 500mg per day, DIM. 

She took a break from her bioidentical hormones initially. Still, the vascular surgeon agreed the clots were due to structural issues and not increased coagulation due to HRT use. She is now back on hormone therapy. Apixaban is prescribed for the next year due to stent placement. She will also be resuming intravenous EDTA treatments to remove the gadolinium. She has returned to exercise, and almost all symptoms have resolved. She will continue to be monitored twice per year with an ultrasound to check the patency of the stent. 

Discussion

This case involved compression of the subclavian and axillary veins, reducing blood flow, which is diagnosed as vTOS with venous thrombosis. Typically, with neurogenic forms, surgery is avoided, opting to correct the issue with physical therapy and lifestyle changes. When the thrombus is involved, like in this case, surgery is typically the best option to avoid catastrophic damage. Time is also of the essence in these cases.  

This case study shows that vTOS is not readily picked up when patients present to the emergency room with objective findings and positive clinical history. A consensus on treating and confirming the diagnosis is inconsistent across specialties in the allopathic community. This condition can present symptoms that bleed into disciplines such as neurology, orthopedics, vascular, cardiology, physical therapy, and pulmonology. This is akin to treating tick-borne infections requiring multiple disciplines because of multisystemic involvement and difficulty in patients finding accurate diagnoses, leading to treatment delays with debilitating impacts on patient quality of life. 

Seeing vascular-related illness has become more common since COVID, and the D-Dimer test has become a standard test measured more than ever with elevated results in patients related to COVID as well as other causes of cardiovascular inflammation. D-Dimer measures the degradation of clots with proteins found in plasma, which can be elevated most with venous thrombosis, cancer, strokes, heart attacks, infections, and other inflammatory conditions.¹⁰ The data is inconsistent about its usefulness as a marker to confirm vascular events such as DVT. The strategy of either imaging or the D-Dimer being performed seems to leave out pertinent data by not using them to entirely rule out a clotting emergency, especially when a patient presents with acute onset pain and swelling of a limb, non-localized to a specific muscle group with discoloration. The D-dimer plus ultrasound can be a non-invasive, reduced-risk, and low-cost combination to assess the presence of a clot. It is something naturopathic physicians in most licensed states can order for our patients if there is a concern. In almost every case, this would require referral to a vascular specialist. Naturopathic medical support can reduce clot formation with a complementary approach of prescribing anticoagulants with nutraceutical support, improve post-surgical healing time, assist patients with lifestyle changes, and prevent future clotting events.

Although not used to identify a thrombotic event, Troponin levels are elevated during acute crises. It was not at the level associated with myocardial infarction, but does leave the question of why it was elevated. 

The treatment goals in this case were to improve blood viscosity, reduce pathogen load, support the patient in reducing sympathetic tone, and enable the patient to resume regular daily routine quickly. The bonus of acquiring a tick-borne disease was an insult to injury with the patient’s recovery, and more so than in other cases, she was infected with two pathogens she had recovered from over a decade prior. 

Babesiosis and Lyme disease can increase injury to the inner lining of the blood vessel, the glycocalyx, and trigger clotting behavior in red blood cells. Babesiosis can utilize mechanisms for sequestration, an initial process leading to the attachment of infected erythrocytes to the endothelial cells of small capillaries. This involves the interaction of parasite molecules at the erythrocyte surface attaching to the endothelial wall, which is called margination. It’s a defense mechanism to gather infected cells into nest-like structures, reducing microvascular blood flow and enhancing clot formation. It essentially pulls the infection out of the bloodstream but causes secondary issues.  This can cause secondary “compensated hypotension,” leading to shortness of breath and dizziness commonly seen in patients with Babesiosis.¹¹

The treatment combination of Arakoda (tafenoquine), an 8-aminoquinolone medication, effectively eradicates atovaquone-resistant Babesia microti and Babesia duncani.  Also, the combination of atovaquone with tefenoquine shows more impressive outcomes with a resolution of infection and possible ongoing immunity if there is future exposure.¹²  G6PD levels must be run before administering tafenoquine to avoid hemolytic anemia.  Methemoglobin levels should also be checked for treatment times longer than 4-6 weeks. The patient tolerated treatment well, with only mild nausea in the first week. Treatment of tafenoquine is usually 200mg for three days, then 200mg once weekly for another five weeks. Treatment times can vary depending on patient response. Utilizing this combination is important, with Babesiosis being the most rapidly growing tick-borne infection in the United States. 

The spread of bacteria via the bloodstream to our vital organs causes most mortality due to bacterial infection. The bacteria must exit the bloodstream and enter organs by resisting the forces generated by flowing blood to adhere to the endothelial cells lining blood vessels without being washed away. Lyme disease pathogen Borrelia burgdorferi exploits an abundant constituent of blood called plasma fibronectin to form endothelial interactions that become stronger as shear forces increase with tethering and bonds made with proteins along the endothelial surface. They then pass through the vessel walls and move through the extracellular matrix to settle in organ systems like the heart wall, kidneys, lungs, and liver. There are also different processes depending on the strain of Borrelia acquired. This also increases inflammatory cascades, furthering clotting factors and leading to venous/arterial thrombosis.¹ Increased vascular injury and clotting factors are more like secondary reactions due to increased inflammation due to the presence of the infection. In this case, the patient was compromised with more heightened vascular inflammation where Borrelia might amplify. 

Healthy blood viscosity and vascular healing are supported with L-citruline, a nitric oxide precursor, vitamin D⁸, diosmin/hesperidin⁵, and baby aspirin. In cases where the patient is not on prescription blood thinners, lumbrokinase, garlic, and nattokinase will be added, a future treatment after completing a year with Apixaban. 

Anti-inflammatory management with low-dose naltrexone¹³ and fractionated marine lipid concentrate² is needed to decrease inflammation, pain, and swelling.  Methylene Blue also uses anti-infective treatment to reduce the persistence of Lyme disease.⁴ Methylene blue was also chosen to support serotonin pathways, improve mitochondrial function, improve shortness of breath, and address the side effects of methemoglobinemia potential with tafenoquine. 

Conclusion

The hope in writing this article is to assist practitioners with proper diagnosis and appropriate referrals to treat the rare but severe presentation of the venous form of thoracic outlet syndrome. This case also gives some guidance on anti-infective strategies for Lyme disease and Babesiosis. Other treatment pathways and options are also proven effective with treatment but were not needed for this patient to recover fully. The good news is that even with complications and delays in diagnosis, the patient has made an almost complete recovery in six months, integrating multiple modalities. It’s also important to point out that the author of this article was the case presented.

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