Brachial Plexopathy Following High-Dose Melphalan and Autologous Peripheral Blood Stem Cell Transplantation for AL Amyloidosis

Brachial plexopathy (also known as neuralgic amyotrophy or Parsonage-Turner syndrome) is a rare, self-limited condition characterized by bilateral or unilateral shoulder pain followed by weakness. The pathogenesis is unknown, but is believed to be an immune-mediated disorder that is treated conservatively with analgesics and physical therapy (PT). It has been described following viral infections, surgeries, and immunosuppression. There has never been a reported case following high dose melphalan and stem cell transplantation (HDM/SCT) for immunoglobulin light chain (AL) amyloidosis.

Here we report two cases of brachial plexopathy following HDM/SCT for AL amyloidosis. These cases were prospectively identified from a population of 42 patients who underwent HDM/SCT at Boston Medical Center between January 2014 and June 2017.

The first patient was a 68-year-old woman with AL amyloidosis with renal involvement with a lambda clonal plasma cell dyscrasia. She was diagnosed with AL amyloidosis three months prior to HDM/SCT. She had no history of peripheral neuropathy or other neurologic disorder. Neutrophil engraftment post-SCT occurred on day +9. On day +12, she developed acute onset bilateral shoulder pain and weakness, left greater than right. Neurologic evaluation at the time was notable for 4/5 strength in the left deltoid, triceps, and biceps muscles. Sensation to pinprick was decreased on the dorsum of the left hand. Deep tendon reflexes were normal. These deficits were consistent with C5-8 motor and sensory dysfunction. Magnetic resonance imaging (MRI) of the cervical spine and brachial plexus and electromyography/nerve conduction study were consistent with bilateral brachial plexopathy. Doppler ultrasounds of the upper extremities were negative for deep venous thrombosis. Lyme disease and West Nile virus testing were negative. She began treatment with PT and her symptoms completely resolved at two years following HDM/SCT.

The second patient was a 58-year-old woman with Waldenström's macroglobulinemia (WM) and associated AL amyloidosis with renal involvement with an underlying lambda clonal plasma cell dyscrasia. She was initially diagnosed with WM eight years prior to her diagnosis of AL amyloidosis. She received eight cycles of rituximab, cyclophosphamide, vincristine, and prednisone for treatment of WM, and then four cycles of rituximab, bortezomib, and dexamethasone after diagnosis of AL amyloidosis. She then underwent HDM/SCT. She had a history of lower extremity peripheral neuropathy secondary to prior treatments, but had no other neurologic symptoms. Neutrophil engraftment occurred on day +10 post-SCT. On day +13, she developed acute onset left shoulder pain and weakness. MRI of the cervical spine and left brachial plexus was consistent with brachial plexopathy. Her symptoms completely resolved by one year post-SCT with PT.

These two cases of brachial plexopathy following HDM/SCT are, to our knowledge, the first reported cases in association with AL amyloidosis. Previously, a handful of cases of brachial plexopathy with similar time courses have been described after both autologous and allogeneic PBSCT in association with multiple myeloma, non-Hodgkin's lymphoma, myelodysplastic syndrome, diffuse large B-cell lymphoma, and multiple sclerosis.^1-3 An autoimmune process has been postulated, especially given the known phenomenon of immune dysregulation following SCT with immune reconstitution. Direct trauma was not a contributing factor in these cases, and both patients had an internal jugular tunneled venous catheter on the right side. We conclude that brachial plexopathy is an uncommon, but potential early complication of HDM/SCT for AL amyloidosis that should be considered in patients with new onset shoulder pain or weakness. PT may be beneficial to patients with this self-limited disorder.

References

1. Rabinstein AA, Dispenzieri A, Micallef IN, et al. Acute neuropathies after peripheral blood stem cell and bone marrow transplantation. Muscle Nerve . 2003;28:733-736.

2. Parrish C, Ming A, Patmore R, et al. Brachial plexopathy following high-dose melphalan and autologous peripheral blood stem cell transplantation. Bone Marrow Transplantation. 2010;45:951-952.

3. Walker M, Zunt JR, and Kraft GH. Brachial plexopathy after immunosuppression and stem cell transplantation for multiple sclerosis. Multiple sclerosis. 2005;11:90-91.