Neurogenic Thoracic Outlet Syndrome and other
Forms of Cervical Brachial Syndrome Treated
with Plasma Concentrate Enriched for Alpha 2
Macroglobulin
Authors: Iovine Jessica Juliet 
Published: March 2021

Background: Existing therapies for myofascial and neuralgic forms of cervicobrachial pain may have
unsatisfactory outcomes. Alternative therapies may be considered, particularly for individuals who have
failed to respond. Contemporary conceptualizations of chronic pain mechanisms include the contribution
of inflammatory factors; therefore, locally targeted antiinflammatory administrations may play a role in
treatment of cervicobrachial pain.
Alpha 2 macroglobulin (A2M) is a plasma protein that acts as a molecular trap for inflammatory factors
such as tumor necrosis factor. After plasma is enriched for A2M, it may be considered as a possible
injectable agent to counteract inflammation that may occur with a cervicobrachial pain syndrome.
Objectives: This retrospective review evaluates patient response to the use of plasma concentrate
enriched for alpha 2 macroglobulin (A2M-PPP) in treatment of neurogenic thoracic outlet syndrome (TOS)
and other forms of cervical brachial syndrome.
Study Design: Observational Study.
Setting: Outpatient interventional neurology practice.
Methods: There were 62 patients, including 46 women and 16 men ages 23-77 years. Twenty-three
of these patients were diagnosed with complex regional pain syndrome (CRPS) or fibromyalgia, 18 with
TOS, and 21 with musculotendinous pain (MTP). At baseline, 1 month, 3 months, and 6 months, patient
status was evaluated with a Brief Pain Inventory (BPI) that included a composite pain score and a functional
interference score. Patients were asked to estimate overall satisfaction with a Patient Global Impression of
Change (PGIC) scale. Criterion for clinically significant improvement included >30% betterment in the BPI
pain and functional interference subscales and a PGIC of > 5 at the 3-month mark.
Results: Three patients, one with CRPS and 2 with TOS, complained of several days of worsened pain
or dysesthesias. No serious or permanent complications were encountered. For patients with TOS at the
3-month mark, 61% achieved clinical endpoints of success compared with 35% with CRPS/fibromyalgia
and 24% for patients with MTP (P < 0.05, chi-square). By 6 months, 22% of individuals in the neuropathic
TOS group had > 30% improvements in pain and functional interference scores compared with 13% of
the individuals in the CRPS/fibromyalgia group and 18% in the MTP group.
Limitations: This article does not differentiate the added benefit of A2M-PPP from hydrodissection alone.
Additionally, this article does not evaluate the actual benefit of the A2M molecule apart from other factors
present in the platelet-poor concentrate such as exosomes and cytokines. With the advent of pure engineered
A2M, more focused studies will be possible. Also, an independent assay was not done, and therefore we
cannot be precisely sure about the exact quantity of platelets, if any, which were contained in the platelet-poor
concentration.
Conclusions: Results suggest that A2M-PPP, when injected into muscle, tendon, and epineurium with
live ultrasound guidance, appears to be relatively safe and free of postinjection inflammatory reactions that
are often seen after platelet-poor plasma injection. A2M-PPP appears to be associated more frequently
with good outcomes when injected into brachial plexus targets in patients with TOS compared with
outcomes observed after injection of the plexus in patients with CRPS/fibromyalgia.
Key words: Plasma concentrate enriched for alpha 2 macroglobulin, neurogenic thoracic outlet
syndrome, cervical brachial syndrome