- Email: [email protected]
Cochlear implantation in a pediatric patient with thalassemia major
Auris Nasus Larynx 36 (2009) 594–597 www.elsevier.com/locate/anl
Cochlear implantation in a pediatric patient with thalassemia major D. Popova *, T.M. Popov Department of ENT, Medical University Sofia, Sofia, Bulgaria Received 20 September 2008; accepted 11 December 2008 Available online 26 February 2009
Abstract We report the first known cochlear implantation in a pediatric patient with thalassemia major. After bilateral profound hearing loss was diagnosed a cochlear implantation was performed in the right ear when he was 24 months old. No complications occurred during the surgery and the postoperative period. Free-field audiometry and evaluation of auditory responses to speech (EARS) battery tests were used to evaluate perceptual auditory abilities, speech recognition and language growth. The patient demonstrated encouraging improvement in threshold levels that reached similar values to those of his peers. In contrast his level of language growth and recognition stayed at low levels. Results are discussed in the light of the specificity of this hereditary disease and its complications as we share our experience for better management of those type of patients in future. # 2009 Elsevier Ireland Ltd. All rights reserved. Keywords: Cochlear implantation; Thalassemia major; Audiometry; Hereditary disease
1. Introduction
2. Case report
Thalassemia is a hereditary anemia resulting from defects in hemoglobin (Hb) production [1]. This medical entity is clinically heterogeneous because there are more than 200 point mutations possible and, rarely, few deletions [2]. Betathalassemia major as a clinical diagnosis is caused by severe mutations in two beta-globin genes which lead to a serious decrease in the production of beta-globin chains. The anemia that is associated with thalassemia may be severe and is accompanied by ineffective erythropoiesis, with bone expansion and extramedullary hematopoiesis in the liver, spleen, and other sites, such as paravertebral masses [3]. Transfusion therapy, which is the mainstay of treatment, along with iron chelating agents allows normal growth and development and suppresses ineffective erythropoiesis [4]. After a thorough investigation of the published materials, to our knowledge, this is the first case of cochlear implantation in a patient with thalassemia major.
2.1. Clinical history
* Corresponding author at: Department of ENT, Medical University Sofia, blvd. ‘‘Han Pagan’’ 1, BG-1680 Sofia, Bulgaria. Tel.: +359 2 850 58 56; fax: +359 2 851 87 83. E-mail addresses: [email protected] (D. Popova), [email protected] (T.M. Popov).
The subject of this paper is a male born in October 2004 after an uncomplicated pregnancy and delivery. At the end of his first year the patient was diagnosed with betathalassemia and since then he is taking infuses with deferoxamine 5 days a week and every 25 days blood transfusions are made (250 ml per transfusion on average). At the age of one and a half years he was accepted in our clinic for audiological examination of the hearing and a number of tests were run. Patient showed no auditory brainstem response (ABR) to acoustic clicks at maximum presentation levels (100 dBnHL) and distortion product otoacoustic emissions (DPOAE) examination displayed no response. Furthermore the 226-Hz tympanometric findings were normal and the acoustic reflex was absent. Computer tomography (CT) and magnetic resonance imaging (MRI) revealed no anomalies in the anatomical structure of the ear and no extramedullary hematopoiesis in the area. On the basis of those results a profound bilateral sensorineural hearing loss was diagnosed. Serologic and polymerase chain reaction tests helped us to discard the possibility of a perinatal infection with cytomegalovirus. There was no
0385-8146/$ – see front matter # 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2008.12.004
D. Popova, T.M. Popov / Auris Nasus Larynx 36 (2009) 594–597
595
Fig. 1. EARS battery test results.
anamnesis of other viral infections during pregnancy which can cause congenital hearing loss. The patient was suggested for diagnostic genetic testing but the parents refused it thus the etiology of his deafness remained unknown. The child was fitted with hearing aids for both ears and was directed to our rehabilitation center for hearing and speech development. Because of the non-satisfactory results of the performed tests and the overall lack of effect, the patient was appointed for cochlear implantation of the right ear after an official consent was signed by the parents. Perceptual auditory abilities were evaluated using the evaluation of auditory responses to speech (EARS) battery (Fig. 1) and displayed zero score in the easiest test from our battery: the Listening Profile Test (LIP). A detailed description of the EARS test battery can be found in previous papers [5,6]. 2.2. Surgery Prior to the operation a consultation was made with a hematologist and as an addition to the patient’s therapy, a blood transfusion of 300 ml blood was performed 8 days before the operation. Preoperative blood cell count showed red blood cell (RBC) count of 4.35 106 mL 1, hemoglobin 10.8 g/dL, haematocrit (Hct) 33.2%, mean corpuscular volume (MCV) 76.3 fL, mean hemoglobin concentration
(MHC) 24.8 pg and platelets (PLT) 513 109 L 1. A minimally invasive surgical approach was performed with a short retroauricular incision and a 1.2 mm cochleostomy after which the complete electrode array insertion was obtained. Intraoperative measurements showed impedance and neural response telemetry (NRT) reactions suggesting a satisfying function of the inner ear and the implant (Nucleus 24 Contour Advance). During the operation itself no unusual bleeding occurred and the blood pressure levels were stable. The first postoperative RBC count showed: 3.79 106 mL 1, Hb 9.4 g/dL, Hct 27.9%, MCV 73.6 fL, MHC 24.2 pg and PLT 416 109 L 1. 2.3. Cochlear implant performance On the 24th day after the surgical operation a successful hookup and mapping of the device was performed. On the basis of the intraoperative NRT results and the active participation of the child we determined the conventional T and C levels by using the advanced combination encoders (ACE) strategy. We observed a good tolerance regarding the cochlear implant amplification. Patient’s hearing threshold and perception was assessed by free-field audiometry and EARS battery. Rehabilitation began afterwards in our center for hearing and speech development. On the 1st, 3rd, 6th, 12th, 18th months after the first mapping of the cochlear
596
D. Popova, T.M. Popov / Auris Nasus Larynx 36 (2009) 594–597
Fig. 2. Free-field audiometry results.
implant new fitting, free-field audiometry (Fig. 2) and EARS battery tests (Fig. 1) were performed. Results show that for the period of 18 months the free-field threshold of the patient reaches normal levels similar to those of his peers (display responses at 25–40 dB pure tone stimuli from 250 to 8000 Hz on the implanted side). The group of closed-set tests form the EARS battery that evaluate speech and language recognition at a basic level (LIP, Monosyllable Trochee Polysyllable Test (MTP) in three levels of difficulty—3, 6 and 12 mono-, bi- and polysyllabic words) show improvement to maximum scores (100%). In contrast the patient displayed no significant improvement in scores of open-set tests (20–30% at 18th month). Those include a monosyllabic word test, the Languages-specific Sentence Test (LS) and the Glendonald Auditory Screening Procedure (GASP) which evaluate more complex ability of understanding and language growth.
had blood transfusion recently. Therefore we planned every following fitting of the implant to be right after his monthly transfusion and in that way we achieved maximum levels of his active participation. It should be noted that this applies also for the rehabilitation process, especially during the week prior to transfusion. This can be explained by the setting in of ischemic processes due to lowering of the hemoglobin levels and chronic hypoxia [11]. Results of free-field audiometry display rapid improvement in the hearing threshold levels which is an indication that the implant functions without any complications and the auditory perception of the patient is at an excellent level. The satisfying results from the LIP and MTP3/6/12 test also confirm that the child recognizes and understands simple speech configurations at levels close to those of his peers. The low scores in the tests evaluating his comprehension of more complex semantic expressions (monosyllabic word test, GASP, LS) can be explained by a combination of factors. First of all the patient was implanted relatively late—hearing loss was found at one and a half years and he was implanted at the age of two. A correlation between age of implantation and speech recognition has been demonstrated in a considerable amount of publications [6,12]. One should take under major consideration also the fact that the rehabilitation process prior to every blood transfusion is significantly less effective. This important specificity of our patient hinders the adequate rehabilitation procedures and as a consequence the development of his speech perception and language abilities is insufficient and prolonged in time. Factors such as motivation, parental support and training are also very important for the degree of success that the child attains with his implant [13] and the latter are not totally present in this case.
3. Discussion 4. Conclusion Beta-thalassemia major is characterized by reduced stability of the cellular membrane of the erythrocytes and lower levels of intracellular glutathione, resulting in higher rates of haemolysis, especially during surgical procedures [1]. In order to raise the hemoglobin and haematocrit over their basal values an additional blood transfusion was made 8 days before surgery. This time gap allowed the homeostatic stabilization of the patient since haemotransfusions display a variety of negative effects [7]. Another problem we feared was the existence of a chronic hypercoagulable state in patients with thalassemia major [1,8]. This persistent anomaly in hemostasis has been recognized as a possible factor for compromised surgical outcome [9,10]. Despite that the hematologic counseling in our case did not suggest that any additional procedures are necessary to be undertaken. Finally no complications such as thromboembolic or ischemic phenomena occurred intra- and postoperatively. A specific finding of ours was the lack of concentration and decreased cognitive functions when the child had not
We report the first known patient with thalassemia major who has received cochlear implantation. We consider that thalassemia major should not be a contraindication for cochlear implantation in patients with severe hearing loss. Still special emphasis should be laid on the need of more intensive rehabilitation than normally performed and a finer control of the hemoglobin levels should be a primary target in therapy.
Conflict of interest Both authors report no conflict of interest in the publication of the article.
Acknowledgements Both authors provided substantial input into the conceptualization, drafting and editing of this report. Each
D. Popova, T.M. Popov / Auris Nasus Larynx 36 (2009) 594–597
has given approval for the publication of the article. There was no funding source for the research.
References [1] Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med 2005; 353:1135–46. [2] Higgs DR, Thein SL, Woods WG. The molecular pathology of the thalassaemias. In: Weatherall DJ, Clegg B, editors. The thalassaemia syndromes. 4th ed., Oxford, England: Blackwell Science; 2001 . p. 133–91. [3] Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR. Complications of b-thalassemia major in North America. Blood 2004;104:34–9. [4] Old JM, Olivieri NF, Thein SL. Diagnosis and management of thalassaemia. In: Weatherall DJ, Clegg B, editors. The thalassaemia syndromes. 4th ed., Oxford, England: Blackwell Science; 2001 . p. 630–85. [5] Gstoettner WK, Hamzavi J, Egelierler B, Baumgartner WD. Speech perception performance in prelingually deaf children with cochlear implants. Acta Otolaryngol 2000;120:209–13.
597
[6] Baumgartner WD, Pok SM, Egelierler B, Franz P, Gstoettner W, Hamzavi J. The role of age in pediatric cochlear implantation. Int J Pediatr Otorhinolaryngol 2002;62:223–8. [7] Heiss MM. Risk of allogeneic transfusions. Br J Anaesth 1998;81(Suppl. 1):16–9. [8] Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood 2002;99:36–43. [9] Cappellini MD, Grespi E, Cassinerio E, Bignamini D, Fiorelli G. Coagulation and splenectomy: an overview. Ann NY Acad Sci 2005;1054:317–24. [10] Miniati DN, Padidar AM, Kee ST, Krummel TM, Mallory B. Portal vein thrombosis after laparoscopic splenectomy: an ongoing clinical challenge. JSLS 2005;9:335–8. [11] Monastero R, Monastero G, Ciaccio C, Padovani A, Camarda R. Cognitive deficits in beta-thalassemia major. Acta Neurol Scand 2000;102:162–8. [12] Nikolopoulos TP, O’Donoghue GM, Archbold S. Age at implantation: its importance in pediatric cochlear implantation. Laryngoscope 1999;109:595–9. [13] Hamzavi J, Baumgartner WD, Egelierler B, Franz P, Schenk B, Gstoettner W. Follow up of cochlear implanted handicapped children. Int J Pediatr Otorhinolaryngol 2000;56:169–74.
Cochlear implantation in a pediatric patient with thalassemia major D. Popova *, T.M. Popov Department of ENT, Medical University Sofia, Sofia, Bulgaria Received 20 September 2008; accepted 11 December 2008 Available online 26 February 2009
Abstract We report the first known cochlear implantation in a pediatric patient with thalassemia major. After bilateral profound hearing loss was diagnosed a cochlear implantation was performed in the right ear when he was 24 months old. No complications occurred during the surgery and the postoperative period. Free-field audiometry and evaluation of auditory responses to speech (EARS) battery tests were used to evaluate perceptual auditory abilities, speech recognition and language growth. The patient demonstrated encouraging improvement in threshold levels that reached similar values to those of his peers. In contrast his level of language growth and recognition stayed at low levels. Results are discussed in the light of the specificity of this hereditary disease and its complications as we share our experience for better management of those type of patients in future. # 2009 Elsevier Ireland Ltd. All rights reserved. Keywords: Cochlear implantation; Thalassemia major; Audiometry; Hereditary disease
1. Introduction
2. Case report
Thalassemia is a hereditary anemia resulting from defects in hemoglobin (Hb) production [1]. This medical entity is clinically heterogeneous because there are more than 200 point mutations possible and, rarely, few deletions [2]. Betathalassemia major as a clinical diagnosis is caused by severe mutations in two beta-globin genes which lead to a serious decrease in the production of beta-globin chains. The anemia that is associated with thalassemia may be severe and is accompanied by ineffective erythropoiesis, with bone expansion and extramedullary hematopoiesis in the liver, spleen, and other sites, such as paravertebral masses [3]. Transfusion therapy, which is the mainstay of treatment, along with iron chelating agents allows normal growth and development and suppresses ineffective erythropoiesis [4]. After a thorough investigation of the published materials, to our knowledge, this is the first case of cochlear implantation in a patient with thalassemia major.
2.1. Clinical history
* Corresponding author at: Department of ENT, Medical University Sofia, blvd. ‘‘Han Pagan’’ 1, BG-1680 Sofia, Bulgaria. Tel.: +359 2 850 58 56; fax: +359 2 851 87 83. E-mail addresses: [email protected] (D. Popova), [email protected] (T.M. Popov).
The subject of this paper is a male born in October 2004 after an uncomplicated pregnancy and delivery. At the end of his first year the patient was diagnosed with betathalassemia and since then he is taking infuses with deferoxamine 5 days a week and every 25 days blood transfusions are made (250 ml per transfusion on average). At the age of one and a half years he was accepted in our clinic for audiological examination of the hearing and a number of tests were run. Patient showed no auditory brainstem response (ABR) to acoustic clicks at maximum presentation levels (100 dBnHL) and distortion product otoacoustic emissions (DPOAE) examination displayed no response. Furthermore the 226-Hz tympanometric findings were normal and the acoustic reflex was absent. Computer tomography (CT) and magnetic resonance imaging (MRI) revealed no anomalies in the anatomical structure of the ear and no extramedullary hematopoiesis in the area. On the basis of those results a profound bilateral sensorineural hearing loss was diagnosed. Serologic and polymerase chain reaction tests helped us to discard the possibility of a perinatal infection with cytomegalovirus. There was no
0385-8146/$ – see front matter # 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2008.12.004
D. Popova, T.M. Popov / Auris Nasus Larynx 36 (2009) 594–597
595
Fig. 1. EARS battery test results.
anamnesis of other viral infections during pregnancy which can cause congenital hearing loss. The patient was suggested for diagnostic genetic testing but the parents refused it thus the etiology of his deafness remained unknown. The child was fitted with hearing aids for both ears and was directed to our rehabilitation center for hearing and speech development. Because of the non-satisfactory results of the performed tests and the overall lack of effect, the patient was appointed for cochlear implantation of the right ear after an official consent was signed by the parents. Perceptual auditory abilities were evaluated using the evaluation of auditory responses to speech (EARS) battery (Fig. 1) and displayed zero score in the easiest test from our battery: the Listening Profile Test (LIP). A detailed description of the EARS test battery can be found in previous papers [5,6]. 2.2. Surgery Prior to the operation a consultation was made with a hematologist and as an addition to the patient’s therapy, a blood transfusion of 300 ml blood was performed 8 days before the operation. Preoperative blood cell count showed red blood cell (RBC) count of 4.35 106 mL 1, hemoglobin 10.8 g/dL, haematocrit (Hct) 33.2%, mean corpuscular volume (MCV) 76.3 fL, mean hemoglobin concentration
(MHC) 24.8 pg and platelets (PLT) 513 109 L 1. A minimally invasive surgical approach was performed with a short retroauricular incision and a 1.2 mm cochleostomy after which the complete electrode array insertion was obtained. Intraoperative measurements showed impedance and neural response telemetry (NRT) reactions suggesting a satisfying function of the inner ear and the implant (Nucleus 24 Contour Advance). During the operation itself no unusual bleeding occurred and the blood pressure levels were stable. The first postoperative RBC count showed: 3.79 106 mL 1, Hb 9.4 g/dL, Hct 27.9%, MCV 73.6 fL, MHC 24.2 pg and PLT 416 109 L 1. 2.3. Cochlear implant performance On the 24th day after the surgical operation a successful hookup and mapping of the device was performed. On the basis of the intraoperative NRT results and the active participation of the child we determined the conventional T and C levels by using the advanced combination encoders (ACE) strategy. We observed a good tolerance regarding the cochlear implant amplification. Patient’s hearing threshold and perception was assessed by free-field audiometry and EARS battery. Rehabilitation began afterwards in our center for hearing and speech development. On the 1st, 3rd, 6th, 12th, 18th months after the first mapping of the cochlear
596
D. Popova, T.M. Popov / Auris Nasus Larynx 36 (2009) 594–597
Fig. 2. Free-field audiometry results.
implant new fitting, free-field audiometry (Fig. 2) and EARS battery tests (Fig. 1) were performed. Results show that for the period of 18 months the free-field threshold of the patient reaches normal levels similar to those of his peers (display responses at 25–40 dB pure tone stimuli from 250 to 8000 Hz on the implanted side). The group of closed-set tests form the EARS battery that evaluate speech and language recognition at a basic level (LIP, Monosyllable Trochee Polysyllable Test (MTP) in three levels of difficulty—3, 6 and 12 mono-, bi- and polysyllabic words) show improvement to maximum scores (100%). In contrast the patient displayed no significant improvement in scores of open-set tests (20–30% at 18th month). Those include a monosyllabic word test, the Languages-specific Sentence Test (LS) and the Glendonald Auditory Screening Procedure (GASP) which evaluate more complex ability of understanding and language growth.
had blood transfusion recently. Therefore we planned every following fitting of the implant to be right after his monthly transfusion and in that way we achieved maximum levels of his active participation. It should be noted that this applies also for the rehabilitation process, especially during the week prior to transfusion. This can be explained by the setting in of ischemic processes due to lowering of the hemoglobin levels and chronic hypoxia [11]. Results of free-field audiometry display rapid improvement in the hearing threshold levels which is an indication that the implant functions without any complications and the auditory perception of the patient is at an excellent level. The satisfying results from the LIP and MTP3/6/12 test also confirm that the child recognizes and understands simple speech configurations at levels close to those of his peers. The low scores in the tests evaluating his comprehension of more complex semantic expressions (monosyllabic word test, GASP, LS) can be explained by a combination of factors. First of all the patient was implanted relatively late—hearing loss was found at one and a half years and he was implanted at the age of two. A correlation between age of implantation and speech recognition has been demonstrated in a considerable amount of publications [6,12]. One should take under major consideration also the fact that the rehabilitation process prior to every blood transfusion is significantly less effective. This important specificity of our patient hinders the adequate rehabilitation procedures and as a consequence the development of his speech perception and language abilities is insufficient and prolonged in time. Factors such as motivation, parental support and training are also very important for the degree of success that the child attains with his implant [13] and the latter are not totally present in this case.
3. Discussion 4. Conclusion Beta-thalassemia major is characterized by reduced stability of the cellular membrane of the erythrocytes and lower levels of intracellular glutathione, resulting in higher rates of haemolysis, especially during surgical procedures [1]. In order to raise the hemoglobin and haematocrit over their basal values an additional blood transfusion was made 8 days before surgery. This time gap allowed the homeostatic stabilization of the patient since haemotransfusions display a variety of negative effects [7]. Another problem we feared was the existence of a chronic hypercoagulable state in patients with thalassemia major [1,8]. This persistent anomaly in hemostasis has been recognized as a possible factor for compromised surgical outcome [9,10]. Despite that the hematologic counseling in our case did not suggest that any additional procedures are necessary to be undertaken. Finally no complications such as thromboembolic or ischemic phenomena occurred intra- and postoperatively. A specific finding of ours was the lack of concentration and decreased cognitive functions when the child had not
We report the first known patient with thalassemia major who has received cochlear implantation. We consider that thalassemia major should not be a contraindication for cochlear implantation in patients with severe hearing loss. Still special emphasis should be laid on the need of more intensive rehabilitation than normally performed and a finer control of the hemoglobin levels should be a primary target in therapy.
Conflict of interest Both authors report no conflict of interest in the publication of the article.
Acknowledgements Both authors provided substantial input into the conceptualization, drafting and editing of this report. Each
D. Popova, T.M. Popov / Auris Nasus Larynx 36 (2009) 594–597
has given approval for the publication of the article. There was no funding source for the research.
References [1] Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med 2005; 353:1135–46. [2] Higgs DR, Thein SL, Woods WG. The molecular pathology of the thalassaemias. In: Weatherall DJ, Clegg B, editors. The thalassaemia syndromes. 4th ed., Oxford, England: Blackwell Science; 2001 . p. 133–91. [3] Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR. Complications of b-thalassemia major in North America. Blood 2004;104:34–9. [4] Old JM, Olivieri NF, Thein SL. Diagnosis and management of thalassaemia. In: Weatherall DJ, Clegg B, editors. The thalassaemia syndromes. 4th ed., Oxford, England: Blackwell Science; 2001 . p. 630–85. [5] Gstoettner WK, Hamzavi J, Egelierler B, Baumgartner WD. Speech perception performance in prelingually deaf children with cochlear implants. Acta Otolaryngol 2000;120:209–13.
597
[6] Baumgartner WD, Pok SM, Egelierler B, Franz P, Gstoettner W, Hamzavi J. The role of age in pediatric cochlear implantation. Int J Pediatr Otorhinolaryngol 2002;62:223–8. [7] Heiss MM. Risk of allogeneic transfusions. Br J Anaesth 1998;81(Suppl. 1):16–9. [8] Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood 2002;99:36–43. [9] Cappellini MD, Grespi E, Cassinerio E, Bignamini D, Fiorelli G. Coagulation and splenectomy: an overview. Ann NY Acad Sci 2005;1054:317–24. [10] Miniati DN, Padidar AM, Kee ST, Krummel TM, Mallory B. Portal vein thrombosis after laparoscopic splenectomy: an ongoing clinical challenge. JSLS 2005;9:335–8. [11] Monastero R, Monastero G, Ciaccio C, Padovani A, Camarda R. Cognitive deficits in beta-thalassemia major. Acta Neurol Scand 2000;102:162–8. [12] Nikolopoulos TP, O’Donoghue GM, Archbold S. Age at implantation: its importance in pediatric cochlear implantation. Laryngoscope 1999;109:595–9. [13] Hamzavi J, Baumgartner WD, Egelierler B, Franz P, Schenk B, Gstoettner W. Follow up of cochlear implanted handicapped children. Int J Pediatr Otorhinolaryngol 2000;56:169–74.