Online ISSN : 1687-8329

    




Quick Search 
 
Author  
Year    
Title  
Vol:  

 
 
July2007 Vol.44 Issue:      2 Table of Contents
Full Text
PDF


Visual Function Evaluation of Egyptian Beta-Thalassemia Major Patients on Long-Term Desferal Therapy

Ann A. Abdel Kader1, Mona H. Abou El-Ela2, Sahar Abd Al-Atty3, Hossam Al-Din Khalil4, Mona Mohamed Nada1

Departments of Clinical Neurophysiology1, Pediatric2, Chemical Pathology3, Cairo University; Ophthalmology4, Beni Suef University

 



ABSTRACT

The success of the iron chelator desferal (DFO) in the treatment of beta - thalassemia is limited by its lack of bioavailability. Also, high dosage has been associated with toxicity of the eyes, ears and others. To investigate a possible subclinical visual neurotoxicity, 30 Egyptian p-thalassemia major (BTM) patients on long-term, recommended DFO dosage were studied using visual evoked potentials (VEPs) and electroretinogram (ERG). We also aimed to clarify the relation of the possible abnormalities to various clinical, hematologic and biochemical parameters. Ten healthy age - matched individuals were enrolled as controls. Sixteen/30 (53.3%) patients showed subclinical abnormalities using VEP and/or ERG. Nine/30 (30%) had VEPs abnormalities, 10 (33.3%) had ERG abnormalities and 3 (10%) revealed abnormalities by both methods. An interesting observation was the significant association of abnormal VEP and sex (P=0.0002). No significant correlation was found between neurophysiologic abnormalities and all data studied as: age, frequency of blood transfusion, DFO dosage/ duration, splenectomy, CBC values; S. ferritin, Serum Copper, S. Zinc and S. vitamin E. A single patient could have subclinical DFO-induced visual toxicity using VEP as his "toxicity" index (TI) was high (0.078). conclusion: the abnormalities can not be mostly attributed to long-term DFO therapy. Serial visual monitoring (including VEP and ERG) of all BTM patients is warranted. It is worthwhile to compare the long-term toxicity of the oral chelating agents (e.g. L 1 & ICL670) with that of DFO before definite conclusions are drawn on any visual neurotoxicity and its relation with the disease state or drug therapy.

(Egypt J. Neurol. Psychiat. Neurosurg., 2007, 44(2): 683-692)

 




NTRODUCTION

 

Patients with β-thalassemia major (BTM) develop iron overload from chronic blood transfusion and require regular iron chelation to prevent potentially fatal iron -related complications1. Desferoxamine (DFO), a hexadentate chelator marked a break through in the treatment of P-thalassemia. It significantly reduces body iron burden and related morbidity and mortality2,3. DFO is still the only most effective drug for general use in the treatment of transfusion dependent iron overload. However, it is expensive, orally inactive and requires long subcutaneous infusions. Moreover, some patients are unable to tolerate DFO and compliance with the drug is poor in many4,5. To obtain an iron balance S.C. DFO daily infusion of 40-60 mg/kg body weight, 5-6 days a week is the treatment of choice6. Also, DFO is associated with many toxic effects such as toxicity of auditory system (high - frequency sensori- neural hearing impairment, tinnitus, acute aphasia) and ocular system (lens opacities, visual loss, loss of color vision, night blindness, visual field defects, dyschromatopsia)7. It had been recognized that most DFO toxic effects have been observed with high doses7-9. However, Olivieri and Brittenham10, strongly recommended regular evaluation of DFO toxicity in all patients maintained on any DFO dose.

Some studies revealed subclinical DFO - induced neurotoxicity in the auditory, visual and other neural pathways in (3-thalassemia patients, using brain stem auditory evoked potentials (BAEP), pattern reversal visual evoked potential (PR-VEP), electroretinogram (ERG), electrooculogram (EOG) and other evoked potentials7,11,12. Deficiency of vitamin E or trace metals (Cu, Zn) has been demonstrated in some chronically transfused patients with BTM13. In some studies depletion of the above trace metals has been related with DFO - induced ocular toxicity2.

 

Aim of Work:

The main goal of this study was to investigate the possible subclinical neurotoxicity in the visual pathway of BTM patients under long - term, standard DFO dosage, using VEPs & ERG. We also aimed to clarify the relation between the possible abnormalities and the following factors: age, sex, dosage & duration of DFO, splenectomy, S. ferritin, S. CU, S. Zn, S. Vitamin E.

 

SUBJECTS AND METHODS

 

This work included 30 patients with BTM, aged 7-18ys,mean 12.7±4.2, 17 ♂ and 13 ♀ with ♂:♀ ratio 1.3 along with 10 healthy age and sex matched individuals as a control group. Patients were recruited from the Hematology Clinic, Pediatric Hospital, Cairo university. All patients were on long - term transfusion - DFO chelation therapy. Duration of DFO treatment ranged from 3-16 years (mean 7.6±4.6ys), dosage ranged from 20-50 mg /kg /day (mean 30.719.1) by S.C DFO pump, 5-6 days a week. The control group comprised 5 q and 5 Q, mean age!3.5±5.1ys.

 

Exclusion Criteria included:

-        Age < 7 years.

-        I.V. or S.C DFO dosage exceeding recommended regimen.

-        Drugs known or suspected to cause visual toxicity.

-        Past history suggestive of DFO related toxicity.

-        Oral chelators or BMT (Bone marrow transplant).

-        D.M or abnormal glucose tolerance test.

-        Clinical visual problem.

-        Neurologic affection.

-        Chronic renal failure (CRF).

-        Clinical liver impairment.

-        Clinical cardiac involvement. All participants were subjected to:

-        Thorough history including family history of visual affection.

-        Full clinical examination with emphasis on manifestations, complications and treatment of BTM. None had vitamin C therapy.

-        Complete ophthalmologic examination including: visual acuity; color vision; examination of the anterior segment, posterior segment and fundi. Others as required e.g. visual field.. .etc.

-        CBC by coulter counter.

-        Reticulocyce count by brilliant cresyl blue.

-        S.Cu and S.Zn by atomic absorption spectrometer.

-        S. Vitamin E by spectrophotometry.

-        Pattern visual evoked potentials evaluation.

-        Pattern - electroretinogram assessment.

 

Other investigations as indicated e.g. Echocardiography, radiological studies, liver function tests.... etc. Blood samples withdrawn pretransfusion and simultaneously with visual pathways evaluation.

Patients wore their lenses during neurophysiologic assessment.

 

PERG:

Both PVEP & ERG testing were done using a NIHON KOHDEN Neuropack 2: The used stimulator was pattern display T.V: video monitor VD 40/A (NIHON KOHDEN). The electrodes used were silver chloride disc electrodes.

The active electrode was placed on the middle of the lower eye lid and was connected to positive grid of the input box. The reference electrode was placed on the ipsilateral temple which was connected to the negative grid of the input box. The ground electrode was placed on the forehead. The electrode impedance was kept below 5000 Ohms. The filter band pass was adjusted at 0.5-100 Hz. The analysis time was adjusted at 300 msec.

Running the test: The stimulus was an alternating checker board pattern. The check size was 16mm, and the contrast (defined as a difference between the maximum and minimum luminance divided by their sum) was presented at 100%. Stimulus rate was adjusted at 2 Hz, 100 stimuli were averaged and repeated twice to ensure reliability and reproducibility. The test was carried with normal size pupil in room light (Neon light). The subject was seated at a distance of 1 meter, from the stimulator and was asked to fix on a small spot placed in the center of monitor.

 

Recording:

The picked up signals were magnified through amplifiers and digitized through an "ADC" convertor. The waves were summed up and averaged of 100 stimuli using a digital computer. The final averaged potentials were displayed on a screen and printed out.

Measurements: The Nl (LI) latency was measured from the stimulus onset to the peak of the first negative deflection (negative down). The PI (L2) latency was measurement from the stimulus onset to the peak of the first positive deflection (positive up) while the amplitude was measured from the isoelectic line to the peak of the positive wave. N2 (L3) latency was measured from the stimulus onset to the peak of the second negative wave.

 

PVEPs:

Those with visual acuities less than 6/18 had their visual EPs testing while wearing their corrective glasses. The apparatus used was the same used in PERG stimuli. Pattern-shift stimuli were presented by a television (T.V) monitor. These were white/black checks. The subjects were asked to fix their gaze at a fixation point in the center of the T.V. screen. Each response represented an averaged summation of 100 stimuli. The responses were elicited after right and left and binocular stimulation.

 

Recording:

The responses were picked up by surface disc electrode applied to the scalp. The electrodes-impedance was kept below 5000 ohm. Three electrodes were used including an active electrode placed 5 cm above the external occipital protuberance in the midline, a reference electrode placed on the right ear lobule and a ground electrode placed on the middle of the forehead. One channel was used to record from the active electrode.

 

Procedure:

The values used for checkerboard stimulation were as follows:

1-             Check Size 16.

2-             Rate of reversal 1 cycle/sec.

3-             Contrast 100%.

 

Data analysis:

1-      Amplitude data were derived by measuring the maximal N75-P100 peak to peak amplitude of each averaged evoked potential.

2-      The latency data P 100 was measured at the first major positive (up ward) deflection P 100.

 

Statistical Design:

The data were analyzed using SPSS package version 10. The results were analyzed using the student's - t-test, Chi square test, Fisher's exact test, as well as a logestic regression method. The data were considered significant if p-values < 0.05.

Latency data of PERG or PVEP were considered abnormal when > the cut off value (> 2 SD of the mean of the controls). While the amplitude data were abnormal if < the cut off value (i.e. < 2 SD of the mean of the control group).

 

RESULTS

 

The current study comprised 30 BTM patients, mean age 12.714.2 (range 7-18ys), 17 ♂ and 13 ♀. All were on prolonged DFO chelation therapy for 3 to 16 ys, mean 7.33±4.5 ys and mean dosage 30.719.1 mg/kg/d (range 20-50 mg/kg/d) by S.C pump, 5-6 days a week. Ten healthy age & sex matched individuals enrolled as controls. All patients had normal eye examination apart from long standing error of refraction in 5/30 (16.7%) patients, corrected by glasses.

Table (1) presents VHP and ERG data in BTM patients and controls. Although for each neurophysiologic method applied there were individual patients expressing abnormal values (as defined in patients & methods), no significant difference was found between the mean latency and amplitude of both VEP & ERG VS controls (P>0.05). According to the cut off values, 16/30 (53.3%) patients had abnormal VEP and/or ERG. VEPs assessment revealed abnormality among 9/30 patients (30%), one had no response of the left eye as well as abnormal amplitude of the Rt. eye. Fig. (1) Three had abnormal latency bilaterally, 3 had unilateral abnormality of the amplitude, one patient had abnormal amplitude bilaterally and another had abnormal latency on one side.

Ten/30 BTM patients (33.3%) had abnormal ERG. Five had bilateral abnormal amplitude associated with bilateral abnormal latency in one patient (LI) Fig. (2) and unilateral abnormal latency in another one (L2, Rt). Four patients had unilateral abnormal amplitude. A single patient showed unilateral abnormal latency (LI, Lt). Three/30 (10%) patients revealed abnormalities of both VEP and ERG.

Figure (3) demonstrates visual pathway defects for each neurophysiologic method applied. There was no association between subclinical visual dysfunction and clinical data as age, freq. of Bl. T, pallor, hepatomegaly, splenomegaly, DFO dosage/ duration and splenectomy. However, sex was highly significantly related to VEP abnormalities as well as to VEP and / or ERG abnormality (Fisher's exact test, P = 0.0002 and 0.004 respect) (Table 2).

Table (3) shows comparative study of age and biochemical parameters in patients and controls. All values revealed statistically significant difference among both categories apart from age.

Table (4) presents clinical and biochemical values in relation to VEPs and ERG. No significant relationship between neurophysiologic abnormalities and all data studied.

A single patient was suspected to have subclinical DFO induced visual toxicity by VEP, as his "toxicity" index (TI) was high [ TI defined as mean daily dose of DFO (mg/kg) divided by S. ferritin level (ng/ml)].

It is reported that TI should not exceed 0.025 (10). In this child it was 0.078 . This patient also had low S. cu (< 2SD of mean of control) and normal S zn.

Table (5): Depicts CBC and neurophysiologic findings in BTM patients. No significant association between CBC parameters and abnormal visual function using VEPs and ERG.

Logestic regression analysis revealed that q gender was the only possible predictor (risk factor) of abnormal VEP (P = 0.01) as well as of VEP and / or ERG abnormalities (P = 0.025). Meanwhile, no significant relationship was observed between visual pathway abnormalities and all other possible risk factors as Age, dose of DFO/ its duration, splenectomy, S. CU, S. Zn, S. Vit E, S. ferritin.


 

Table 1. YEP and ERG hi BTM patients and controls (mean±SD).

 

Parameter

BTM (No=30)

Control (No=10)

P-value

VEP (visual evoked potentials)

 

 

 

 

 

 

 

     * Latency (ms)

 

 

 

 

 

 

 

Rt

 

102.5±10.4

 

98.2±5.100

 

0.218

 

Lt

 

100.8±21.5

 

103.7±6.7

 

0.676

 

      * Amplitude (fiv)

 

 

 

 

 

 

 

Rt

 

18.7±12.1

 

15.1±3.3

 

0.363

 

Lt

 

16.4±7.9

 

13.6±3.2

 

0.277

 

ERG (electroretinogram)                                 

      * Latency (ms)

 

 

 

 

 

 

L1      Rt

 

24.1±4

 

26.5±1.5

 

0.096

 

L1      Lt

 

25.1±3.7

 

27.3±1.5

 

0.071

 

L2      Rt

 

51.1±1.4

 

51.5±1.4

 

0.380

 

L2      Lt

 

514.±0.8

 

51.9±1.5

 

0.3

 

L3      Rt

 

102.7±4.1

 

102.9±5.5

 

0.907

 

L3      Lt

 

102.5±4.1

 

101.2±4.9

 

0.402

 

      *Amplitude (uv)

 

 

 

 

 

 

 

L1L2  Rt

 

2.1±1.4

 

2±0.4

 

0.848

 

L1L2  Lt

2.2±1.4

 

2.1±0.5

 

0.919

 

 

Table 2. Comparison of neurophysiologic abnormality regarding sex.

 

Parameter

(n=17)

(n=13)

P-value

No of cases

%

No of cases

%

VEP abnormality

(n=9)

8

47.10

1

7.70

0.0002 (HS)

ERG abnormality

(hf= 10)

7

41.20

3

23.10

0.08 (NS)

VEP and/or ERG abnormality (n-16)

 

12

70.60

4

30.80

0.004 (S)

 

Table 3. Comparison of age and Biochemical variables among thalassemic patients and controls.

 

Parameter

 

BTM (n=30)

 

Controls (n= 10)

 

P-values

 

Age (years)

 

12.70±4.2

 

13.5±5.1

 

0.623 (NS)

 

S. ferritin (ng/ml)

 

2100±888.1

 

32.1±12.9

 

0.000 (HS)

 

S.Vit. E (mg/L)

 

2.6±2.2

 

9.1±2.6

 

0.000 (HS)

 

S. Cu (µg/d!)

 

136.3±25.7

 

242.3±30.7

 

0.000 (HS)

 

S. Zn (µg/dl)

 

85.1±19

 

109.2±21.9

 

0.005 (S)

 

P>0.05= not significant (NS), P<0.05 = significant (S), P<0.001= highly significant (HS)

 

 

Table 4. Clinical and Biochemical Values in relation to VEPs & ERG in BTM (n=30).

Parameter

Age (ys)

Freq Of blood T. (wk)

Daily DFO dose (mg/kg)

Duration of DFO (ys)

 

S, ferritin (ng/ml)

S.cu

(µg/dl)

S.Zn (µg/dl)

S. Vile E (mg/L)

ERG

Abnormal

 

10

 

13±3.9

 

4.7±0.95

 

32.7±12.7

 

6.0±1.1

1672.2±620

 

138.8±29.7

 

85.4±25.1

 

3.0±3.1

 

Normal

 

20

 

12.5±4.4

 

4.3±0.97

 

293±5.1

 

8.2±5.7

 

2084,6±98I3

 

128.1±19.4

 

85±!5.9

 

23±1.65

p-value

 

 

 

0.717

 

0.24

 

0.48

 

0364

 

0.24

 

0.1

 

0.96

 

0.46

 

VEP

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Abnormal

 

9

 

14.3±5.3

 

4.2±0.8

34.5±7.2

 

6.0±1.1

 

1.744.3±841.5

 

138.1±34-3

 

75.9±20.8

 

3±3.1

 

Normal

21

12±3.5

4.5±1.03

28.3±9.04

8.2±5.7

2033.8±913.6

135.6±22.1

89.1±17.2

2.4±1.7

p- value

 

 

 

0.163

 

0.52

 

0.173

 

0364

 

0.423

 

0.809

 

0.080

 

0.5

 

VEP and/or ERG

 

Abnormal

 

16

 

13.6±4.6

 

4.6±1.02

 

30.23±8.6

 

7.6±5.51

 

1704±775.8

 

141.9±30.8

 

83.5±20.9

 

2.8±2.7

 

Normal

 

14

 

I1.7±3.5

 

43±0.99

 

31.35±9.6

 

7.±3.7

 

2224.6±954.1

 

130±173

 

87±17.05

 

23±1.6

 

p-value

 

 

 

0.231

 

0.367

 

0.818

 

0.823

 

0.1.11

 

0.213

 

0.247

 

0.6

 

 

Table 5. C.B.C. in patients (n=30) as regards VEP & ERG abnormalities.

 

Parameter

No

HB (g/dl) |  (X1012/L)

Hct%

WBCs

(X109/L)

Plal (XIO'YL)

Retic%

ERG

Abnormal

 

10

 

6.95±1.19

 

3.24±0.4 6

 

2l.98±1.66

 

14.24±5.97

 

493.8±163.8

 

4.09±2.9

 

Normal

 

20

 

7.58±0.92

 

3.11±0.35

 

22.80±3.10

 

13.5±5.1

 

456.3±21I.5

 

5.05±3.3

 

P- value

 

 

 

0.121

 

0.398

 

0.432

 

0.737

 

0.627

 

0.240

 

VEP

Abnormal

 

9

 

7.34±0.82

 

3.25±0.35

 

23.2±3.3

 

14.48±5.8

 

521.9±174.3

 

5.7±2.9

 

Normal

 

21

 

7.4±1.14

 

3.11±0.41

 

22.3±2.4

 

13.5±5.2

 

446±202.6

 

4.3±3.1

 

P- value

 

 

 

0.932

 

0.394

 

0.383

 

0.640

 

0.337

 

0.175

 

VER & ERG

Abnormal

 

16

 

7.08±1.09

 

3.2±0.39

 

22.54±2.77

 

14.14±5.96

 

492.9±174.8

 

4.6±2.7

 

Normal

 

14

 

7.7±0.92

 

3.09±0.39

 

22.5±2.7

 

13.3±4.6

 

441.4±218.8

 

4.8±3.55

 

P- value

 

 

 

0.106

 

0.423

 

0.995

 

0.666

 

0.477

 

0.877

 

 

 

Fig. (1): VEP of BTM patient; no response of left eye and abnormal amplitude

of Rt. Eye (1.05 µv, cut off value=8.4 µv ).

 

 

Fig. (2): ERG of BTM patient; bilateral abnormal latency (L1, both 34.2ms, cut of value 92.5 Rt. and 30.2 Lt. ms) and bilateral abnormal amplitude (Rt 0.31 and Lt 0.49 µv, cut off value 1.2 and 1.3 µv respect).

 

 

Fig. (3): Visual abnormalities among BTM patients using VEP and ERG.


DISCUSSION

 

Beta-thalassemia Is an inherited blood disorder which through repeated blood transfusions & enhanced iron uptake from the gastro intestinal tract, results in marked iron overload. Untreated, the iron accumulation results in the dysfunction of vital organs such as the heart & liver. The most effective treatment of B-thalassemia is the iron chelator, DFO, which is expensive, orally inactive & requires long S.C infusions14,15.

High doses of DFO that exceed the recommended range of 40-60 mg/kg/d, by LV. or S.C route have been associated with toxicity to the eyes & ears16. However, many authors strongly recommended evaluation of DFO toxicity in all patients maintained on any doses of DFO10,17.

We investigated possible subclinical neurotoxicity of the visual pathway of BTM children on long-term and recommended DFO dosage, using VEPs and ERG. We also aimed to investigate the relationship between the possible abnormalities and all clinical and laboratory data studied.

The current study revealed subclinical visual abnormalities by ¥EP and ERG in 30% and 33.3% of patients respectively, meanwhile, 53.3% of patients showed abnormalities using one and/or the other method. Other investigators reported nearly similar results3,7,8.

An interesting observation was the highly significant association between VEP abnormalities and sex (P = 0.0002). This could be due to associated inherited abnormality affecting males mainly and/or exposure to substances or toxins to which ♀ are not exposed or due to poor compliance to DFO among VS ♀. However, large scale studies are needed to clarify this observation and its etiology.

Giardina & Grady3 reported that, splenectomy may improve DFO efficiency in previously fiypersplenic patients & help achieve iron balance, while, Zaheiriou et al.6 reported that splenectomy is a risk factor for abnormal visual pathway in BTM. On the other hand, our study showed 0,0 significant association between splenectomy & abnormal results. This discrepancy could be the result of involvement of many factors in the achievement of iron balance.

We were able to study vitamin E, Zn & Cu serum levels simultaneously with the neurophysiologic studies, thus eliminating any variations in the serum levels of these substances during the study period. Serum Cu, S-Zn & S. vitamin E levels were significantly lower in BTM patients VS controls (P<0.01) while S. ferritin levels ware significantly higher than controls (P = 0.000). This is in concordance with other authors13.

The present investigation showed insignificant correlation between neurophysiologic abnormalities and all clinical & laboratory data as: age fireq. of BI. T, DFO dose/ duration, CBC values, S. ferritin, S. Zn, S.Cu & S. Vitamin E. So, visual abnormalities was mostly independent of standard DFO therapy, similar to other authors6,7,18.

It has been suggested19 that dictation of metals other than iron (Zn, Cu) could have been responsible for the ocular toxicity of high - dose I.V. DFO. De virgiliis and Coworkers20, observed transient & permanent ERG abnormalities in 10/14 (71.4%) thalassemia patients with high-dose IV DFO infused over a short period of time. These defects were related to Zinc & Copper or iron depletion.

However, as mentioned above, with standard DFO therapy, no correlation was found between subclinical visual abnormalities using VEPs or ERG and S.Cu, S. Zn or S. Vitamin E levels.

In the present research, visual abnormalities could be the result of the disease itself along with chronic hypooxygenation of BTM children6,16.

Some studies reported that persistent iron overload could contribute to visual toxicity as the DFO dosage used was at the lower suggested limit13,21.

Congenital visual pathway abnormalities not affecting vision may contribute to some BTM patients with subclinical visual abnormalities as the neurophysiologic evaluation was not applied before DFO therapy.

This study revealed a single patient who could have subclinical DFO — induced visual abnormalities using VEP. His DFO dose = 50 mg/kg/d, S. ferritin = 640 ng/ml (low iron burden) and "toxicity" index= 0.078 (high), S. Zn was normal and S. Cu low when visual abnormalities were observed. Olivieri and Brittenham10 recommended that if hepatic iron concentration can not regularly assessed, a "toxicity" index, defined as the mean daily dose of DFO (mg/kg) divided by the serum ferritin concentration (ng/ml) should be calculated for each patient every 6 months, and should not exceed 0.025.

The mechanism of DFO toxicity has not been fully elucidated. Theories generally fall into one of 3 categories. Direct inhibition of the iron dependent enzymes as ribonucleotide redtictase, essential for DNA synthesis22. Chelation from tissue of critical trace elements other than iron, such as Cu &  Zh19,20. A result of free radical formation by DFO. DFO displays a dose-related biphasic antioxidant- praoxidant behavior. At high concentrations, DFO can amplify oxidizing damage through generation of hydroxyl radicals23.

 

Conclusion & Recommendation

Sixteen / 30 BTM patients had subclinical visual pathway abnormalities using VEPs and/or ERG. These abnormalities can not mostly attributed to standard, long-term DFO — therapy.

One patient only had suspected DFO mediated subclinical visual abnormality using VEP.

Serial visual monitoring of all BTM patients is warranted, (including VEP & ERG).

It is worthwhile to compare the long-term toxicity of the oral chelating agents, like deferiprone (LI) and ICL 670, with that of DFO in thalassemic children before definite conclusions are drawn on any visual neurotoxicity and its relationship with the disease state or the effect of drug therapy. Some studies (24-27) reported zinc deficiency with Li therapy which may be associated with retinal abnormalities.

Further large scale studies are recommended to clarity the significant association between sex and subclinical visual abnormality as well as its etiology.

REEFRENCES

 

1.      Barman Ball our JA and Foster RH (1999): Deferiprone: a review of its clinical potential in iron overload in beta thalassemia major and other transfusion dependent diseases. Bruges: 58.553-78.

2.      Brittenham GM, Griffith PM, Nienhuis AW, Mclaren CE, Young NS, Tucker EE, et al: (1994): Efficacy of desferioxamine in preventing complications of iron overload in patients with thalassemia major. N. Engi J med 331:567 -573.

3.      Giardina P J and Grady RW (1995): Chelatioe therapy in p-thalassonia: The benefits and limitations of desferrioxamine. Seminars in Hematology. 32: 304-312.

4.      Galanello R, Piga A, Alberti D, Rouan MC, Bigler H and Sechaud R (2003): Safety, Tolerability, and PharmacOkinetics of ICL 670, a new orally active iron -chelating agent in patients with transfusion — dependent iron overload due to beta - thalassemia. J-Clin - Parmacol. 63:563-72.

5.      Nick H, Acklin P, Lattman R, Buehlmayer P, Hauffe S, Schupp J et al (2003): Development of tridentate iron chelators: from desferrithiocin to ICL 670. Curr — Med- Chem 10: 1065 - 76.

6.      Zafeiriou D I, Kousi A, Tsantali CT, Kontopoulos EE, Augoustidou - Sawopoulou PA, Tsoubaris PD et al (1998). Neurophysioiogic Evaluation of long — term DFO therapy B-thalassemia. Pediatr Neurol. 18:420-24.

7.      Wong V, LiA & Lee ACW (1993): Neurophysiolgoical study of B- thalassemia patients. J Child Neurol. 8: 33^5.

8.      Olivieri NF, Buncic JR, Chew E, Gallant T, Hairison RV, Keenan K et al (1986): Visual and Auditory Neurotoxicity in patients receiving subcutaneous DFO infusions. N Engl J Med. 314: 869 -73.

9.      Porter JB, and Huehns El (1989): The toxic effects of DF6. Baillier"s Clin Hematol. 2:459.

10.    Olivieri NF and Brittenham GM (1997): lion -chelating therapy and the treatment of thalassemia. Blood. 89:739-76L

11.    Marciani MG, Cianciulli P, Stefanini F, Petoni L, Sabbadini M, et al (1991): Toxic effects of high dose DFO therapy in patients with iron over load: on electrophysiolgical stud of cerebral and visual function Hematologica. 76: 131^4.

12.    Kontazoglou G, Koussi A, Tsatra J et al (1996): Sensorineural hearing loss in chidren with thalassemia major in Northern Greece. Int J Pediat otorhinolaryngoL 35:223-30.

13.    MC Donagh K and Nieuhuis A (1993): The thalassemias: In. Nathan DG, OSki FA eds. Hematology of infancy and childhood. 4th edL Philadelphia MB sounders. 674-95.

14.    Wong. C. and Richardson DR. (2003): Beta thalassemia: emergence of new and improved iron chelators for treatment Int - J- Biocehm- Cell Biol. 35: 1144-9.

15.    Alymara V, Bourantas D, Chaidos A, Bouranta P, Gouva M, Vassou A, et al (2004): Effectiveness and safety of combined iron - chelation therapy with desferoxamine and deferiprone Hemotol. J. 5: 475-9.

16.    Jiang- C, Hansen RM, Gee BE, Kurth SS and Fulton AB, et al (1999): Rod and Rod mediated function in patients with B-thalassemia major Doc- OphthalmoL 96: 33-45.

17.    Fbsburg MT and Nathan DG (1990): Treatment of Cooley Anemia. BloodL 76.435-43.

18.    Rinaldi M, Delia Corte M, Ruocco V, O'Onofiio CD, Zanotta G and Romano A, (1993): Ocular involvement correlated with age in patients Affected by Major and intermedia B. thalassemia treated or not with DFO. Metabolic Pediatric and systemic ophthalmology. 16.23-25.

19.    Levine JE, Cohen A, Mac Queen M, Martin M and Giardina PJ (1997): Sensorimotor Neurotoxitity Associated with High - Dose DFO treatment J. Pediatr Hemat Oncology. 19:139-141.

20.    Devirgitii S, Congia M, Turco MP, Frau F, Dessi C, Argiolu F, Sorcinelli R, et al (1988): Depletion of trace elements and acute ocular toxicity induced by DFo in patients with lhalassemia Arch Dis child. 63:250-5.

21.    Britton RS, Leicester KL and Bacon BR (2002): Iron toxicity and chelation therapy. Int-J Hemalal 76: 219: 28.

22.    Singh S, Khodr H, Taylor M I and Hider RC (1995): Therapeutic iron chelators and their potential side - effects. Biochem - Soc- Symp. 61: 127.

23.    Esposito B-P Breuer W, Sirankapracha P, Pootrakul P. Hershko C and Cabantchik 71 (2003): Labile Plasma iron in iron overload: redox activity & susceptibility to chelation. Blood. 102:2670-7.

24.    Al- Refaie FN, Heishko C, Hoflbrand AV, Kosaryan M, Olivieri NF, Tondury P et al (1995): Results of long - term deferipone (LI) therapy a report by the international study group on oral iron chelators Bn. 1 — Hematol. 91:224-9.

25.    Barman - Balfour JA & Raster RH (1999): Deferiprone a review of its clinical potential in mm overload in beta thalassemian major and other transfuskMi dependent diseases Drugs. 58:553-78.

26.    Cohen AR, Galanello R, Piga A, Dipalma A, Vullo C and TRicta F (2000): safety profile of the oral iron dieolor deferipone: a multicentre study. Br. J. HematoL 108:305-12.

27.    Voskaridou E, Douskou M, Teipos E, Stamoulakatou A, Meletis J, Ouiailidis A et al (2005): Deferiprone as an oral iron chelator in sickle cell disease. Ann. Hematol. 84 434-40.


 

الملخص العربى

 

تقييم وظيفة الابصار لدى المرضى المصريين المصابين  بمرض أنيميا البحث المتوسط

والذين يعالجون بعقار الديسفرال لمدة طويلة

 

نجاح الديسفرال (العقار المخلص من الحديد الزائد بالجسم) فى علاج أنيميا البحر المتوسط يحده نقص تواجده الحيوى بالجسم وكذلك الجرعات العالية منه تعتبر مرتبطة بسميه فى العين والأذن وأجزاء أخرى.

ولبحث إمكانية وجود تسمم عصبي بصري غير واضح إكلينيكياً , تم دراسة 30 مريض مصري مصاب بأنيميا البحر المتوسط يعالج بالديسفرال لمدة طويلة وبالجرعات المتعارف عليها وذلك باستخدام جهد المسار البصري والرسم الكهربائى لشبكية العين. ويهدف هذا البحث أيضاً إلى توضيح العلاقة المحتملة بين القياسات الشاذة والعوامل  الإكلينيكية والدموية وكذلك الحيوية.

 



2008 � Copyright The Egyptian Journal of Neurology,
Psychiatry and Neurosurgery. All rights reserved.

Powered By DOT IT