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Acute Lower Extremity Paralysis Following Radiation Therapy for Cervical Cancer
Gynecologic Oncology 75, 152–154 (1999) Article ID gyno.1999.5561, available online at http://www.idealibrary.com on
CASE REPORT Acute Lower Extremity Paralysis Following Radiation Therapy for Cervical Cancer Nadeem R. Abu-Rustum, M.D.,* Dharma Rajbhandari, M.D.,† Silvio Glusman, M.D.,‡ and L. Stewart Massad, M.D.* *The Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, †Department of Radiation Oncology, and ‡Department of Anesthesia and Pain Service, Cook County Hospital, Chicago, Illinois 60612 Received January 27, 1999
CASE REPORT
Background. Acute lower extremity paralysis secondary to lumbosacral plexopathy is a rare but severe complication that may follow pelvic radiotherapy for cervical cancer. Case. A 49-year-old female with newly diagnosed stage IIIB cervical cancer developed progressive bilateral lower extremity paralysis and pelvic pain only 10 weeks following completion of radiation therapy for cervical cancer with no evidence of metastasis or progression of disease. Her bladder and bowel function were not affected. Following extensive workup, the most likely etiology was presumed radiation-induced lumbosacral plexopathy. Conclusion. Although metastatic carcinoma is more commonly the reason for progressive lower extremity weakness with pelvic pain in women with advanced cervical cancer, radiation-induced lumbosacral plexopathy, a rare but devastating complication, may be the cause. Diagnosis is by exclusion. © 1999 Academic Press Key Words: radiation plexopathy; cervical cancer; pelvic pain.
INTRODUCTION
A 49-year-old African American female, gravida 4, para 4004, was admitted with heavy vaginal bleeding and pelvic pain. Examination was significant for a large friable cervical tumor, 8 cm in greatest diameter. Biopsies confirmed a poorly differentiated squamous cell cervical carcinoma. Chest X ray was negative. Computerized tomography (CT) of the abdomen and pelvis revealed a large cervical tumor with bilateral parametrial invasion and bilateral hydronephrosis, but no significant adenopathy and no evidence of distant metastasis. The patient underwent examination under anesthesia, cystoscopy with bilateral retrograde ureteral stenting, and proctoscopy under intravenous sedation. The examination was compatible with a Stage IIIB cervical carcinoma with bilateral parametrial invasion greater on the left and abutting the pelvic sidewall. Past medical history was significant for hypertension for 16 years maintained with oral agents, asthma for 2 years maintained with bronchodilator inhalers, smoking 5 cigarettes per day for 10 years, and occasional alcohol use. The patient was treated with radiation therapy alone with a curative intent. Between 7/6/98 and 8/17/98, 4500 cGy external radiation was delivered to the pelvis through four fields with a beam energy of 18 MV. The radiation was delivered as 180 cGy per fraction in 25 fractions. This was followed on 8/24/98 by intracavitary radiation with a Fletcher suit that delivered 2500 cGy mean dose to point A and a second implant on 8/31/98 that was abruptly removed by the patient due to discomfort and anxiety after delivering only 762 cGy to point A. Both implants were placed under spinal anesthesia and the patient received postoperative intravenous morphine with a patient-controlled analgesia pump. The patient refused further radiotherapy with a total delivered dose to point A of 7692 cGy and 5464 cGy to point B. The total treatment duration was approximately 8 weeks. Except for the early removal of the second implant, the treatment was tolerated well with decrease
Radiotherapy remains the treatment of choice for locally advanced cervical cancer. Acute lower extremity paralysis is a very rare complication of gynecologic cancer therapy, and the development of lower extremity neuropathy with pelvic pain and progressive bilateral flaccid paralysis following the treatment of cervical cancer is a perplexing diagnostic and therapeutic dilemma. Metastasis or local tumor progression with secondary nerve involvement usually leads the differential diagnosis, particularly in women with advanced cervical cancer, a disease that may involve the pelvic nerves or spread to the spinal/epidural spaces. After excluding neoplastic and other neurologic causes, radiation-induced lumbosacral plexopathy is the presumed diagnosis. We present a case of severe bilateral lower extremity paralysis with pelvic pain that developed only 10 weeks following the completion of external and intracavitary radiation for cervical cancer. 0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.
152
CASE REPORT
in pelvic pain, a urinary tract infection treated with oral antibiotics, and intermittent diarrhea. Ten weeks after completing radiotherapy the patient was readmitted after reported worsening pain, mainly in the buttock region, and bilateral lower extremity weakness, greater on the right side, leaving her unable to walk. The patient was evaluated by gynecologic oncology, neurology, radiation oncology, infectious disease, pain service, and physical therapy. Over a 2-week period she developed flaccid paralysis in both lower extremities with sensory changes over the lateral legs and feet, but her bladder and rectal functions remained intact. Physical exam was significant for resolution of the central tumor with acute radiation changes in the vagina and no obvious parametrial disease except fibrosis. Neurologic exam was significant for bilateral lower extremity weakness greater on the right side, with decreased motor function in hip flexion, knee flexion and extension, and bilateral sensory changes over the lateral legs and both feet with patchy sensory loss. CT scan of the abdomen and pelvis revealed a small cervix with acute radiation changes and no distant metastasis or progression of disease. The lumbosacral plexus appeared normal. Head CT and magnetic resonance imaging (MRI) of the thoracic and lumbar spine were negative. Electromyogram and nerve conduction studies revealed abnormality consistent with L 3, L 4, L 5, S 1, and S 2 radiculopathy. Gallium scan did not reveal any focal inflammatory disease, and bilateral leg Doppler studies were normal. A spinal tap was essentially normal, with no evidence of malignancy, infectious, or inflammatory process. The patient was retested for syphilis, tuberculosis, and human immunodeficiency virus and all results were negative. Complete blood count and serum chemistry showed no abnormality that explained her syndrome. The diagnosis of radiation-induced lumbosacral plexopathy was made by exclusion, and the patient was treated with longand short-acting oral morphine, amitriptyline, gabapentin, and mexiletine for pain control and was discharged to a rehabilitation facility. No neurologic improvement or evidence of recurrence was noted at the time of this report. The neuropathy remained confined to the lower extremities. DISCUSSION It is estimated that 1–2 women per 1000 treated with pelvic radiation for gynecologic malignancies may develop lumbosacral plexopathy with secondary lower extremity weakness. Predisposing factors and the exact mechanism have not been clearly elucidated, but the addition of brachytherapy to teletherapy may be a contributing factor [1]. The majority of reported cases in gynecologic oncology occurred in women with cervical cancer treated with curative intent with both external and intracavitary radiotherapy [1, 2]; however, this neurologic complication was also reported with radiotherapy for endometrial cancer, bladder cancer, and other
153
pelvic solid tumors including preoperative therapy for rectal cancer [3–5]. Thomas et al. [6] outlined the clinical differential diagnosis between radiation-induced and tumor-related plexopathy of the pelvis, with the former presenting as indolent leg weakness that eventually becomes more severe, bilateral, and associated with pain in only one-half of patients, as opposed to the unilateral and usually painful lower extremity weakness that is seen in the majority of tumor-related plexopathies. In addition, Saphner et al. [2] noted that radiation plexopathy characteristically lacks the presence of tumor at diagnosis, is predominantly a motor, bilateral dysfunction, and is associated with long survival. Moreover, metastasis-related neurologic complications in women with cervical cancer were twice as common as nonmetastasis-related neurologic complications, with lumbosacral plexopathy, caused by retroperitoneal lymph node metastasis, being the most common neurologic complication. Exclusion of neoplastic invasion of the lumbosacral plexus is essential and may be accomplished by CT scanning; however, MRI is more sensitive than CT for diagnosing cancerinduced lumbosacral plexopathy [7]. Urinary and rectal function are commonly preserved, although fecal incontinence of presumed lumbosacral plexopathy has been reported in women treated with radiotherapy for cervical cancer [8]. The minimum dose of radiation associated with this complication is undetermined, but the mean radiation dose to the periphery of the pelvic inlet at the level of the lumbosacral plexus was calculated to be 7300 cGy in four women with cervical cancer who developed this complication 8 –24 months following completion of definitive radiotherapy with no evidence of recurrence [1]. The total dose to the lumbosacral plexus in this case was estimated to be 5708 cGy. Of interest is that our patient and the four patients reported by Georgiou and Grigsby did not receive extended field radiotherapy, and all received two intracavitary implants with a total dose to point A of 7503– 8630 cGy, compared to 7692 cGy in our case; however, the short interval between completion of radiation and presentation in this case (10 weeks) is rarely noted [4], as this complication commonly appears 6 months or more following completion of therapy and has been noted as late as 14 years after curative radiotherapy [2, 3]. Pelvic pain, a main presenting complaint in our case, is reported in 1/4 –1/2 of patients with this disease [1, 6] and effective control may be achieved with medical therapy. Radiation-induced lumbosacral plexopathy, a rare but severe complication of pelvic cancer therapy, is rarely encountered by most gynecologic oncologists. Cisplatin, the most active single chemotherapeutic agent in the treatment of cervical cancer with known secondary peripheral neurotoxicity, is currently being used in conjunction with external radiation in advanced-stage disease; therefore, it remains to be determined whether the concomitant use of cisplatin-based chemotherapy with radiation will result in an increase in this neurologic complication.
154
ABU-RUSTUM ET AL.
REFERENCES 1. Georgiou A, Grigsby PW, Perez CA: Radiation induced lumbosacral plexopathy in gynecologic tumors: clinical findings and dosimetric analysis. Int J Radiat Oncol Biol Phys 26:479 – 482, 1993 2. Saphner T, Gallion HH, Van Nagell JR, Kryscio R, Patchell RA: Neurologic complications of cervical cancer a review of 2261 cases. Cancer 64:1147–1151, 1989 3. Aho K, Kimmo S: Late radiation induced lesions of the lumbosacral plexus. Neurology 33:953–955, 1983 4. Ashenhurst EM, Quartey GRC, Starreveld A: Lumbo-sacral radiculopathy induced by radiation. Can J Neurol Sci 4:259 –263, 1977
5. Frykholm GJ, Sintron K, Montelius A, Jung B, Pahlman L, Glimelius B: Acute lumbosacral plexopathy during and after preoperative radiotherapy of rectal adenocarcinoma. Radiother Oncol 38:121–130, 1996 6. Thomas JE, Cascino TL, Earle JD: Differential diagnosis between radiation and tumor plexopathy of the pelvis. Neurology 35:1–7, 1985 7. Taylor BV, Kimmel DW, Krecke KN, Cascino TL: Magnetic resonance imaging in cancer-related lumbosacral plexopathy. Mayo Clin Proc 72:823– 829, 1997 8. Iglicki F, Coffin B, Ille O, Flourie B, Amarenco G, Lemann M, Messing B: Fecal incontinence after pelvic radiotherapy: evidence for a lumbosacral plexopathy. Report of a case. Dis Colon Rectum 39:465– 467, 1996
CASE REPORT Acute Lower Extremity Paralysis Following Radiation Therapy for Cervical Cancer Nadeem R. Abu-Rustum, M.D.,* Dharma Rajbhandari, M.D.,† Silvio Glusman, M.D.,‡ and L. Stewart Massad, M.D.* *The Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, †Department of Radiation Oncology, and ‡Department of Anesthesia and Pain Service, Cook County Hospital, Chicago, Illinois 60612 Received January 27, 1999
CASE REPORT
Background. Acute lower extremity paralysis secondary to lumbosacral plexopathy is a rare but severe complication that may follow pelvic radiotherapy for cervical cancer. Case. A 49-year-old female with newly diagnosed stage IIIB cervical cancer developed progressive bilateral lower extremity paralysis and pelvic pain only 10 weeks following completion of radiation therapy for cervical cancer with no evidence of metastasis or progression of disease. Her bladder and bowel function were not affected. Following extensive workup, the most likely etiology was presumed radiation-induced lumbosacral plexopathy. Conclusion. Although metastatic carcinoma is more commonly the reason for progressive lower extremity weakness with pelvic pain in women with advanced cervical cancer, radiation-induced lumbosacral plexopathy, a rare but devastating complication, may be the cause. Diagnosis is by exclusion. © 1999 Academic Press Key Words: radiation plexopathy; cervical cancer; pelvic pain.
INTRODUCTION
A 49-year-old African American female, gravida 4, para 4004, was admitted with heavy vaginal bleeding and pelvic pain. Examination was significant for a large friable cervical tumor, 8 cm in greatest diameter. Biopsies confirmed a poorly differentiated squamous cell cervical carcinoma. Chest X ray was negative. Computerized tomography (CT) of the abdomen and pelvis revealed a large cervical tumor with bilateral parametrial invasion and bilateral hydronephrosis, but no significant adenopathy and no evidence of distant metastasis. The patient underwent examination under anesthesia, cystoscopy with bilateral retrograde ureteral stenting, and proctoscopy under intravenous sedation. The examination was compatible with a Stage IIIB cervical carcinoma with bilateral parametrial invasion greater on the left and abutting the pelvic sidewall. Past medical history was significant for hypertension for 16 years maintained with oral agents, asthma for 2 years maintained with bronchodilator inhalers, smoking 5 cigarettes per day for 10 years, and occasional alcohol use. The patient was treated with radiation therapy alone with a curative intent. Between 7/6/98 and 8/17/98, 4500 cGy external radiation was delivered to the pelvis through four fields with a beam energy of 18 MV. The radiation was delivered as 180 cGy per fraction in 25 fractions. This was followed on 8/24/98 by intracavitary radiation with a Fletcher suit that delivered 2500 cGy mean dose to point A and a second implant on 8/31/98 that was abruptly removed by the patient due to discomfort and anxiety after delivering only 762 cGy to point A. Both implants were placed under spinal anesthesia and the patient received postoperative intravenous morphine with a patient-controlled analgesia pump. The patient refused further radiotherapy with a total delivered dose to point A of 7692 cGy and 5464 cGy to point B. The total treatment duration was approximately 8 weeks. Except for the early removal of the second implant, the treatment was tolerated well with decrease
Radiotherapy remains the treatment of choice for locally advanced cervical cancer. Acute lower extremity paralysis is a very rare complication of gynecologic cancer therapy, and the development of lower extremity neuropathy with pelvic pain and progressive bilateral flaccid paralysis following the treatment of cervical cancer is a perplexing diagnostic and therapeutic dilemma. Metastasis or local tumor progression with secondary nerve involvement usually leads the differential diagnosis, particularly in women with advanced cervical cancer, a disease that may involve the pelvic nerves or spread to the spinal/epidural spaces. After excluding neoplastic and other neurologic causes, radiation-induced lumbosacral plexopathy is the presumed diagnosis. We present a case of severe bilateral lower extremity paralysis with pelvic pain that developed only 10 weeks following the completion of external and intracavitary radiation for cervical cancer. 0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.
152
CASE REPORT
in pelvic pain, a urinary tract infection treated with oral antibiotics, and intermittent diarrhea. Ten weeks after completing radiotherapy the patient was readmitted after reported worsening pain, mainly in the buttock region, and bilateral lower extremity weakness, greater on the right side, leaving her unable to walk. The patient was evaluated by gynecologic oncology, neurology, radiation oncology, infectious disease, pain service, and physical therapy. Over a 2-week period she developed flaccid paralysis in both lower extremities with sensory changes over the lateral legs and feet, but her bladder and rectal functions remained intact. Physical exam was significant for resolution of the central tumor with acute radiation changes in the vagina and no obvious parametrial disease except fibrosis. Neurologic exam was significant for bilateral lower extremity weakness greater on the right side, with decreased motor function in hip flexion, knee flexion and extension, and bilateral sensory changes over the lateral legs and both feet with patchy sensory loss. CT scan of the abdomen and pelvis revealed a small cervix with acute radiation changes and no distant metastasis or progression of disease. The lumbosacral plexus appeared normal. Head CT and magnetic resonance imaging (MRI) of the thoracic and lumbar spine were negative. Electromyogram and nerve conduction studies revealed abnormality consistent with L 3, L 4, L 5, S 1, and S 2 radiculopathy. Gallium scan did not reveal any focal inflammatory disease, and bilateral leg Doppler studies were normal. A spinal tap was essentially normal, with no evidence of malignancy, infectious, or inflammatory process. The patient was retested for syphilis, tuberculosis, and human immunodeficiency virus and all results were negative. Complete blood count and serum chemistry showed no abnormality that explained her syndrome. The diagnosis of radiation-induced lumbosacral plexopathy was made by exclusion, and the patient was treated with longand short-acting oral morphine, amitriptyline, gabapentin, and mexiletine for pain control and was discharged to a rehabilitation facility. No neurologic improvement or evidence of recurrence was noted at the time of this report. The neuropathy remained confined to the lower extremities. DISCUSSION It is estimated that 1–2 women per 1000 treated with pelvic radiation for gynecologic malignancies may develop lumbosacral plexopathy with secondary lower extremity weakness. Predisposing factors and the exact mechanism have not been clearly elucidated, but the addition of brachytherapy to teletherapy may be a contributing factor [1]. The majority of reported cases in gynecologic oncology occurred in women with cervical cancer treated with curative intent with both external and intracavitary radiotherapy [1, 2]; however, this neurologic complication was also reported with radiotherapy for endometrial cancer, bladder cancer, and other
153
pelvic solid tumors including preoperative therapy for rectal cancer [3–5]. Thomas et al. [6] outlined the clinical differential diagnosis between radiation-induced and tumor-related plexopathy of the pelvis, with the former presenting as indolent leg weakness that eventually becomes more severe, bilateral, and associated with pain in only one-half of patients, as opposed to the unilateral and usually painful lower extremity weakness that is seen in the majority of tumor-related plexopathies. In addition, Saphner et al. [2] noted that radiation plexopathy characteristically lacks the presence of tumor at diagnosis, is predominantly a motor, bilateral dysfunction, and is associated with long survival. Moreover, metastasis-related neurologic complications in women with cervical cancer were twice as common as nonmetastasis-related neurologic complications, with lumbosacral plexopathy, caused by retroperitoneal lymph node metastasis, being the most common neurologic complication. Exclusion of neoplastic invasion of the lumbosacral plexus is essential and may be accomplished by CT scanning; however, MRI is more sensitive than CT for diagnosing cancerinduced lumbosacral plexopathy [7]. Urinary and rectal function are commonly preserved, although fecal incontinence of presumed lumbosacral plexopathy has been reported in women treated with radiotherapy for cervical cancer [8]. The minimum dose of radiation associated with this complication is undetermined, but the mean radiation dose to the periphery of the pelvic inlet at the level of the lumbosacral plexus was calculated to be 7300 cGy in four women with cervical cancer who developed this complication 8 –24 months following completion of definitive radiotherapy with no evidence of recurrence [1]. The total dose to the lumbosacral plexus in this case was estimated to be 5708 cGy. Of interest is that our patient and the four patients reported by Georgiou and Grigsby did not receive extended field radiotherapy, and all received two intracavitary implants with a total dose to point A of 7503– 8630 cGy, compared to 7692 cGy in our case; however, the short interval between completion of radiation and presentation in this case (10 weeks) is rarely noted [4], as this complication commonly appears 6 months or more following completion of therapy and has been noted as late as 14 years after curative radiotherapy [2, 3]. Pelvic pain, a main presenting complaint in our case, is reported in 1/4 –1/2 of patients with this disease [1, 6] and effective control may be achieved with medical therapy. Radiation-induced lumbosacral plexopathy, a rare but severe complication of pelvic cancer therapy, is rarely encountered by most gynecologic oncologists. Cisplatin, the most active single chemotherapeutic agent in the treatment of cervical cancer with known secondary peripheral neurotoxicity, is currently being used in conjunction with external radiation in advanced-stage disease; therefore, it remains to be determined whether the concomitant use of cisplatin-based chemotherapy with radiation will result in an increase in this neurologic complication.
154
ABU-RUSTUM ET AL.
REFERENCES 1. Georgiou A, Grigsby PW, Perez CA: Radiation induced lumbosacral plexopathy in gynecologic tumors: clinical findings and dosimetric analysis. Int J Radiat Oncol Biol Phys 26:479 – 482, 1993 2. Saphner T, Gallion HH, Van Nagell JR, Kryscio R, Patchell RA: Neurologic complications of cervical cancer a review of 2261 cases. Cancer 64:1147–1151, 1989 3. Aho K, Kimmo S: Late radiation induced lesions of the lumbosacral plexus. Neurology 33:953–955, 1983 4. Ashenhurst EM, Quartey GRC, Starreveld A: Lumbo-sacral radiculopathy induced by radiation. Can J Neurol Sci 4:259 –263, 1977
5. Frykholm GJ, Sintron K, Montelius A, Jung B, Pahlman L, Glimelius B: Acute lumbosacral plexopathy during and after preoperative radiotherapy of rectal adenocarcinoma. Radiother Oncol 38:121–130, 1996 6. Thomas JE, Cascino TL, Earle JD: Differential diagnosis between radiation and tumor plexopathy of the pelvis. Neurology 35:1–7, 1985 7. Taylor BV, Kimmel DW, Krecke KN, Cascino TL: Magnetic resonance imaging in cancer-related lumbosacral plexopathy. Mayo Clin Proc 72:823– 829, 1997 8. Iglicki F, Coffin B, Ille O, Flourie B, Amarenco G, Lemann M, Messing B: Fecal incontinence after pelvic radiotherapy: evidence for a lumbosacral plexopathy. Report of a case. Dis Colon Rectum 39:465– 467, 1996