Original ArticlesNeurophysiologic Evaluation of Long-Term Desferrioxamine Therapy in Beta-Thalassemia Patients
Introduction
Desferrioxamine (DFO) is currently used to treat patients who have manifested beta-thalassemia major (BTM) with transfusion-chelation therapy to reduce iron overload. To obtain an iron balance, subcutaneous DFO daily infusion of 40-60 mg/kg 5 to 6 days a week is the current treatment of choice [1].
In the last 15 years, high DFO doses have been associated with toxicity of the auditory system (high-frequency sensorineural hearing impairment, tinnitus, acute aphasia) and ocular system (lens opacities, visual loss, loss of color vision, night blindness, visual field defects, dyschromatopsia) 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. In some of these studies 6, 9, 14, 16, brainstem auditory- evoked potential (BAEP) and visual-evoked potential (VEP) abnormalities have been demonstrated; complete or partial recovery from high-dose DFO neurotoxicity occurred after discontinuation of the drug 9, 10. However, other ocular abnormalities, not related to DFO, have been occasionally reported in BTM patients 17, 18. Subclinical involvement of the somatosensory and peripheral nervous system was neurophysiologically demonstrated, using somatosensory-evoked potential (SEP) and nerve conduction velocity (NCV) studies, in patients with BTM who demonstrated poor compliance regarding DFO therapy [15]. Pathologic results were correlated with higher serum ferritin level and the presence of diabetes mellitus [15], the latter being a common complication in these patients [1]. Deficiency of vitamin E or trace metals (copper, zinc) has been demonstrated in some chronically transfused patients with BTM [1]. In some studies, depletion of the above trace metals has been associated with DFO-induced ocular toxicity 3, 11.
In a systematic neurophysiologic study, possible involvement of the auditory, visual, central somatosensory and peripheral neural pathways in patients with BTM was investigated, using BAEP, VEP, SEP, and NCV studies, respectively. Subsequently, the results were correlated factors such as age, serum ferritin level, DFO dosage, DFO duration, serum copper, zinc, and vitamin E levels, as well as the presence of splenectomy.
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Patients and Methods
All BTM patients 10 years of age and older (n = 40 from a total of 105; 23 boys, 17 girls; age range from 11 to 19 years, mean, 15.2 ± 2.1 years), being treated in the Thalassemia Unit of the First Department of Pediatrics, were selected to enter the study.
All patients were maintained in the transfusion-chelation program. DFO was administered subcutaneously at home, overnight, using a battery-powered syringe pump at least five nights per week. The DFO dosage ranged from 26 to 50 mg/kg/day
Results
Although for each neurophysiologic method applied there were individual patients expressing abnormal values (as defined in the Patients and Methods section), only mean prolongation of interpeak latency I-V of the BAEP and decrease of the sural NCV were found statistically significant (P < 0.05; Table 1) compared with the control group.
Regarding the BAEP, 10 patients (25%) had pathologic findings with prolonged interpeak latencies I-V, and four (10%) patients also had prolonged interpeak
Discussion
In this study, subclinical involvement of the auditory, visual, somatosensory, and peripheral nervous pathways occurred in 25%, 15%, 7.5%, and 25% of the patients, respectively, and 15% of the patients demonstrated involvement of multiple neural pathways.
Auditory neurotoxicity under long-term DFO treatment has occasionally been reported 2, 9, 12, 13, 14, 15, 16. In these studies, auditory symptoms subsided after withdrawal or decrease of DFO. Porter et al. [12] found a significant correlation
Acknowledgements
The authors thank Chrisanthi Angeli, MSc, for statistical assistance.
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