Brentuximab-Induced Peripheral Neuropathy in the Setting of Radiation-Induced Brachial Plexopathy

Peripheral neuropathy is characterized by progressive, debilitating sensory loss and motor dysfunction. Radiation-induced brachial plexopathy (RIBP) causes significant motor disability in approximately 1.2% of patients receiving radiotherapy. The incidence of chemotherapy-induced peripheral neuropathy (CIPN) has increased with the expanded use of chemotherapeutic agents. Brentuximab vedotin (BV), an anti-CD30 monoclonal antibody approved for Hodgkin's lymphoma (HL) in the pediatric population, induces sensory neuropathy. The double crush phenomenon describes two sites of nerve compression along a peripheral nerve, resulting in greater neurological dysfunction than at one site. One example is when CIPN is concomitant with RIBP, although these cases are not well described in the literature. A patient with BV-induced CIPN with concomitant RIBP was seen at our tertiary referral center, which specializes in complex upper extremity care. This case contributes to the literature by describing the diagnosis and clinical characteristics of chemoradiotherapy-related neuropathies and their subsequent management. A 16-year-old male with a history of refractory HL presented with significant right upper extremity weakness. Nine months prior, he had completed 14 rounds of stereotactic body radiotherapy; seven months prior, he had begun maintenance therapy with BV. Within four months of his visit, weakness progressed to his bilateral lower extremities and contralateral upper extremity with mild distal sensory loss. Electromyography and nerve conduction studies evaluating peripheral nerve function demonstrated an asymmetric, non-length-dependent, predominantly motor-sensory polyradiculoneuropathy. MRI of the brachial plexus and cervical spine demonstrated asymmetric thickening of the right C5-C8 nerve roots and trunks with a high T2 signal and subtle enhancement with contrast and no infiltrative neoplastic lesion. Treatment with oral prednisone for four weeks resulted in objective clinical improvement three months after treatment was initiated. Neurotoxic chemotherapeutic agents may potentiate the effects of radiotherapy, resulting in progressive sensory symptoms. BV neurotoxicity may be related to autoimmunity or inhibition of axonal transport. The double crush phenomenon accounts for atypical presentations in patients receiving local radiotherapy or chemotherapeutic agents. Further studies are required to characterize the double crush phenomenon in cancer patients.