Early Post Radiation Neuropathy: Complex Pathogenesis Including Microvasculitis and Tumor Spread
Michael Skolka1, Joon Uhm1, Daniel Ma2, Ashley Santilli1, James Meiling3, Paola Sandroni1, Nathan Staff1, Marcus Vinicius Pinto1, P. James B. Dyck1, Christopher Klein1
1Neurology, 2Radiation Oncology, 3Physical Medicine & Rehabilitation, Mayo Clinic
Objective:
To describe patients with early radiation-induced peripheral nerve injury and investigate potential pathogenic mechanism(s).
Background:
Radiation-induced neuropathy typically occurs up to decades after radiation from neural fibrosis with insidious, painless progressive weakness.  Reports of early radiation-associated neuropathies are lacking.
Design/Methods:
Patient cases labeled as “radiation neuropathy” were electronically retrieved from our electromyography (EMG) and Mayo Data Explorer databases between January 2014 to August 2022.  Inclusion criteria included neural deficits within 6 months of radiation, EMG testing, and available follow-up nerve imaging. 
Results:
Twenty-two patients (9 female, mean age 63 years [range 34-84]) were identified with a history of squamous (n=6), prostate (n=5), breast (n=3), rectal (n=2), hematologic (n=2), and other (n=4) cancers.  Average radiation dose was 4491 cGy (range 1000-7208).  Time to symptom onset averaged 1.9 months (range 0-4). Pre-radiation chemotherapy occurred in most (n=16).  All neuropathies occurred in the same radiation territory, but most neuropathies (n=17) occurred distal to the radiation site.  EMG-confirmed neuropathies included radiculopathies (n=10), brachial and lumbosacral plexopathies (n=10), and mononeuropathies (n=2).  EMG myokymia was seen in few (n=6).  Patients reported primarily painful paresthesias (n=18) and weakness (n=18).  Clinical courses were monophasic (n=8), progressive (n=8), static (n=2), and unclear without follow-up (n=4).  Follow-up neural MRI did not suggest infiltrative disease (n=21), but based on tumor location and progressive course, microscopic infiltration was suspected.  Two patients had nerve biopsies showing prominent inflammation around epineural microvessels with vessel wall injury (microvasculitis).  One biopsy revealed neoplastic spread of rectal squamous cell cancer.  Steroid burst therapy was attempted in 6 patients; 5 reported benefits, and 4 had monophasic courses.
Conclusions:

Early-onset post radiation neuropathies having pain and monophasic courses are supported by steroid response and biopsy-confirmed microvasculitis to have an inflammatory-immune mechanism.  Exclusion of infiltrative cancer and an idiosyncratic radiation injury with progressive course are important to consider. 

10.1212/WNL.0000000000202735