2',3'-DIDEOXYCYTIDINE (DDC) TOXIC NEUROPATHY - A STUDY OF 52 PATIENTS

被引:122
作者
BERGER, AR
AREZZO, JC
SCHAUMBURG, HH
SKOWRON, G
MERIGAN, T
BOZZETTE, S
RICHMAN, D
SOO, W
机构
[1] MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10467
[2] BROWN UNIV,DEPT MED,PROVIDENCE,RI 02912
[3] STANFORD UNIV,DEPT MED,STANFORD,CA 94305
[4] HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110
[5] UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093
关键词
D O I
10.1212/WNL.43.2.358
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We administered the antiviral agent 2',3'-dideoxycytidine (ddC) to HIV-infected patients with either ARC or AIDS as part of the AIDS Clinical Treatment Group protocol 012 and serially evaluated them with neuropathic symptom questionnaires, neurologic examinations, nerve conduction studies, and quantitative sensory testing (QST). All patients treated with high-dose ddC (0.06 and 0.03 mg/kg every 4 hours) developed a painful, predominantly sensory peripheral neuropathy, with a mean onset of 7.7 weeks, which reached severe intensity over several days. Abnormalities of vibration QST thresholds preceded clinical symptoms. Treatment with 0.01 mg/kg every 4 hours produced a similar neuropathy, although of milder severity, later onset (mean, 9.3 weeks), and slower progression. In these patients, the onset of clinical symptoms and QST abnormalities were coincident. Only two of six patients treated with 0.005 mg/kg every 4 hours developed clinical or laboratory evidence of neuropathy; in both cases it was very mild and delayed in onset (26 weeks). All patients treated with high-dose ddC reported progression of symptoms (coasting) for 2 to 3 weeks following discontinuation of therapy. This study documents a painful sensory neuropathy resulting from treatment with ddC. With high-dose treatment, only the rapidity of onset and progression differentiated it from the distal, predominantly sensory neuropathy of AIDS.
引用
收藏
页码:358 / 362
页数:5
相关论文
共 12 条
[1]   SENSORY MOTOR NEUROPATHY ASSOCIATED WITH AIDS [J].
BAILEY, RO ;
BALTCH, AL ;
VENKATESH, R ;
SINGH, JK ;
BISHOP, MB .
NEUROLOGY, 1988, 38 (06) :886-891
[2]   POTENT AND SELECTIVE ANTI-HTLV-III/LAV ACTIVITY OF 2',3'-DIDEOXYCYTIDINENE, THE 2',3'-UNSATURATED DERIVATIVE OF 2',3'-DIDEOXYCYTIDINE [J].
BALZARINI, J ;
PAUWELS, R ;
HERDEWIJN, P ;
DECLERCQ, E ;
COONEY, DA ;
KANG, GJ ;
DALAL, M ;
JOHNS, DG ;
BRODER, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 140 (02) :735-742
[3]  
CHEN C, 1991, AM SOC PHARM EXP THE, V39, P625
[4]   PREDOMINANTLY SENSORY NEUROPATHY IN PATIENTS WITH AIDS AND AIDS-RELATED COMPLEX [J].
CORNBLATH, DR ;
MCARTHUR, JC .
NEUROLOGY, 1988, 38 (05) :794-796
[5]   REVERSIBLE AXONAL NEUROPATHY FROM THE TREATMENT OF AIDS AND RELATED DISORDERS WITH 2',3'-DIDEOXYCYTIDINE (DDC) [J].
DUBINSKY, RM ;
YARCHOAN, R ;
DALAKAS, M ;
BRODER, S .
MUSCLE & NERVE, 1989, 12 (10) :856-860
[6]   POLYNEUROPATHY FOLLOWING VINCRISTINE THERAPY IN 2 PATIENTS WITH CHARCOT-MARIE-TOOTH SYNDROME [J].
HOGANDANN, CM ;
FELLMETH, WG ;
MCGUIRE, SA ;
KILEY, VA .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1984, 252 (20) :2862-2863
[7]  
KEILBAUGH SA, 1990, STRUCTURE FUNCTION B, P159
[8]   CIRCULATING P24 ANTIGEN LEVELS AND RESPONSES TO DIDEOXYCYTIDINE IN HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTIONS - A PHASE-I AND PHASE-II STUDY [J].
MERIGAN, TC ;
SKOWRON, G ;
BOZZETTE, SA ;
RICHMAN, D ;
UTTAMCHANDANI, R ;
FISCHL, M ;
SCHOOLEY, R ;
HIRSCH, M ;
SOO, W ;
PETTINELLI, C ;
SCHAUMBURG, H .
ANNALS OF INTERNAL MEDICINE, 1989, 110 (03) :189-194
[10]  
YARCHOAN R, 1989, NEW ENGL J MED, V321, P726, DOI 10.1056/NEJM198909143211106