Recurrent acute inflammatory demyelinating polyradiculoneuropathy following R-CHOP treatment for non-Hodgkin lymphoma Jackson J. Liang, DO, Preet P. Singh, MD, and Thomas E. Witzig, MD
Acute flaccid paralysis following chemotherapy has a wide differential diagnosis, including drug toxicity, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and malignant nerve infiltration. We present a case of recurrent acute quadriparesis due to AIDP following chemotherapy for non-Hodgkin lymphoma, which resolved each time following administration of intravenous immunoglobulin. Although many chemotherapeutic agents can cause neurologic side effects, such as peripheral neuropathy, drug toxicity as a cause is a diagnosis of exclusion.
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cute flaccid paralysis following chemotherapy has a wide differential diagnosis, including drug toxicity, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and malignant nerve infiltration. We present a case of recurrent acute quadriparesis due to AIDP following chemotherapy for non-Hodgkin lymphoma, which resolved each time following administration of intravenous immunoglobulin (IVIG). CASE PRESENTATION A 62-year-old man with recently diagnosed stage IV diffuse large B-cell lymphoma presented for his first cycle of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The diagnosis had been confirmed by pleural and testicular biopsies. Pretreatment positron emission tomography (PET) scan had revealed diffuse nodal activity and extranodal involvement in the pleura, testicles, and bones (Figure 1a). The patient had been otherwise healthy. He tolerated his first cycle of R-CHOP chemotherapy with no issues. Two days after completing the R-CHOP cycle, he began to notice bilateral lower-extremity weakness, which began at his feet and gradually moved upwards to his hip girdle muscles. The weakness gradually worsened to the point where he needed to use his hands to push off and stand from a seated position. Shortly thereafter, he noted bilateral arm weakness and became unable to stand due to the inability to push off with his arms. He also developed numbness in all four extremities from his mid forearms distally and the knees down. Throughout this time, he retained bowel and bladder function. His severe weakness and
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footdrop prompted a trip to the emergency department, and he was admitted for workup. Examination at this time revealed mild upper-extremity weakness proximally with moderate to severe upper-extremity distal weakness. He had profound lower-extremity weakness, distal worse than proximal. While lying supine, he could move his legs minimally from side to side but was unable to lift them against gravity. He was unable to move his feet at all. Deep tendon reflexes at the knees were markedly diminished bilaterally, and ankle reflexes were completely absent. The Babinski sign was negative. Due to concern for Guillain Barré syndrome, lumbar puncture and electromyography with nerve conduction studies were ordered. Cerebrospinal fluid from the lumbar puncture exhibited albuminocytologic dissociation with an elevated protein (77 g/dL) and a cell count of 1 cell per microliter. Electromyogram revealed diffusely abnormal motor nerve conduction with low amplitude; slow, dispersed compound muscle action potentials; and conduction block in the median, ulnar, tibial, and peroneal nerves. HIV and hepatitis studies were negative. He was diagnosed with AIDP, and IVIG was initiated at 400 mg/ kg/day for 5 days. Shortly after being given the first dose of IVIG, his strength began to improve. Upon awakening the following morning, he was able to raise both knees and his left arm against gravity. By that afternoon, he was able to stand and walk a few steps with a wheeled walker and assistance. Upon completion of the 5-day course of IVIG, the numbness in his forearms and hands had resolved completely. He was discharged to the inpatient rehabilitation unit, where he continued to recover. At discharge after just 4 days of rehabilitation, he was able to ambulate without the assistance of a cane. During his second R-CHOP cycle, the vincristine dose was halved. Afterwards he experienced a brief episode of tingling and mild weakness in his hands and feet, which resolved completely after 48 hours. Follow-up PET scan prior to cycle 3 demonstrated complete radiologic remission (Figure 1b) with From the Department of Medicine (Liang) and the Divison of Hematology and Medical Oncology (Singh, Witzig), Mayo Clinic, Rochester, Minnesota. Corresponding author: Jackson Liang, DO, 200 1st Street SW, Rochester, MN 55905 (e-mail:
[email protected]). Proc (Bayl Univ Med Cent) 2013;26(2):156–158
peripheral nerves. The weakness was not likely due to vincristine or rituximab, as the symptoms developed after the first dose. Furthermore, vincristine toxicity was unlikely as he had a severe recurrence of weakness following his fourth cycle when vincristine was withheld. His malignancy responded extraordinarily to R-CHOP, as his testicles decreased to normal size a few days after his first cycle. Ultimately, his recurrent neurologic symptoms were attributed to AIDP from the underlying lymphoma, as his miraculous rapid improvement with IVIG did not fit with drug toxicity or direct lymphomatous nerve infiltration. Non-Hodgkin lymphoma is the most common cause of lymphomatous neuropathy syndromes (1). Although AIDP is most classically associated with Hodgkin lymphoma (2, 3), non-Hodgkin lymphoma can also cause a clinical picture of AIDP with evidence of demyelination on electromyelography and needle conduction studies. R-CHOP, a frequently used regimen in the treatment of non-Hodgkin lymphoma, has been linked to the Figure 1. (a) Pretreatment PET scan demonstrating diffuse nodal activity and extranodal involvement in the pleura, development of AIDP (4, 5), partictesticles, and bones. (b) Follow-up PET scan prior to R-CHOP cycle 3 demonstrating complete radiologic remission. ularly rituximab (6) and vincristine (7–10). AIDP, the major variant of no sign of lymphomatous involvement of the nerves. Full-dose the group of neurologic disorders commonly referred to by the vincristine was given with his third R-CHOP cycle. After 5 days, eponym “Guillain Barré syndrome,” is believed to be due to he noted complete loss of sensation in his fingers and feet. His autoimmune attack on the myelin of peripheral nerves, leading symptoms resolved over the next few days and were attributed to to electrical conduction slowing and muscular weakness. It is vincristine. As such, vincristine was withheld during his fourth often preceded by an upper respiratory or gastrointestinal tract cycle. Five days following this fourth cycle, he experienced severe infection, most commonly due to Campylobacter jejuni, Epsteinweakness in his legs bilaterally in addition to numbness in his Barr virus, or cytomegalovirus (11). Other systemic illnesses hands and feet, similar to his initial episode of AIDP. A repeat associated with AIDP include HIV, viral hepatitis, sarcoidosis, electromyogram once again demonstrated findings consistent and systemic lupus erythematosus (2). with polyradiculoneuropathy. Lumbar puncture demonstrated The diagnosis is multifaceted. Clinical findings include protein of 98 g/dL with 1 total nucleated cell per microliter. A progressive symmetric muscle weakness and diminished or complete serum and cerebrospinal fluid paraneoplastic panel absent deep tendon reflexes. Lumbar puncture with analysis and cerebrospinal fluid cytology sent at that time were negative. of cerebrospinal fluid typically reveals normal cell count with He was treated again with a 5-day course of IVIG (400 mg/kg/ elevated protein, also known as albuminocytologic dissociaday) with complete resolution of symptoms. tion. Electromyography with needle conduction study is helpful in the diagnosis of AIDP, typically revealing slowing of nerve DISCUSSION conduction with conduction block or abnormal dispersion, The differential diagnosis in our patient’s acute ascending prolonged distal latencies, and delayed F waves (12). weakness included autoimmune AIDP secondary to his underTreatment consists of supportive care and disease-modifying lying lymphoproliferative malignancy, vincristine or rituximab therapy. Up to 30% of patients require mechanical ventilation neurotoxicity, and direct lymphomatous involvement of the due to weakness of muscles of respiration or inability to swallow a
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Recurrent AIDP following R-CHOP treatment for non-Hodgkin lymphoma
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and protect the airway. Plasmapheresis and IVIG are the main therapies for AIDP. Plasmapheresis removes circulating autoantibodies in the blood, while IVIG may neutralize autoantibodies (13) and prevent complement-mediated nerve damage (14). 1. 2. 3. 4.
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6.
7.
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Baylor University Medical Center Proceedings
Volume 26, Number 2
