Elsevier

Pediatric Neurology

Volume 18, Issue 5, May 1998, Pages 420-424
Pediatric Neurology

Original Articles
Neurophysiologic Evaluation of Long-Term Desferrioxamine Therapy in Beta-Thalassemia Patients

https://doi.org/10.1016/S0887-8994(98)00004-6Get rights and content

Abstract

Forty patients with beta-thalassemia major (BTM), between 11 and 19 years of age and maintained on long-term desferrioxamine (DFO) treatment, were examined by evoked potential and nerve conduction velocity studies to investigate a possible involvement of the auditory, visual, somatosensory, or peripheral nervous pathways. Pathologic findings in brainstem auditory-, visual-, and somatosensory-evoked potentials, and nerve conduction velocity studies were demonstrated in 25%, 15%, 7.5%, and 25% of the patients, respectively, whereas 15% demonstrated involvement of multiple neural pathways. Subclinical involvement of the auditory pathway was statistically associated with higher mean daily DFO dose and longer duration of DFO therapy, whereas abnormalities regarding the somatosensory pathways were related to older age, longer mean duration of DFO therapy, and lower serum copper levels. Involvement of the peripheral nervous system was related to lower serum copper levels. Multiple involvement of neural pathways was related to longer mean duration of DFO therapy. We conclude that risk factors related to long-term DFO treatment are only partly responsible for the subclinical involvement of neural pathways demonstrated in beta-thalassemia major 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.

Section snippets

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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