Cochlear implantation in children with Bartter syndrome: A case report

Abstract

Bartter syndrome (BS) is an autosomal recessive disorder characterized by polyhydramnios, premature birth, polyuria, renal salt-wasting, hypokalemic metabolic alkalosis, normal blood pressure with increased levels of renin and aldosterone, and the presence of hearing loss. Mutations in BSND, CLCNKA, and CLCNKB cause the disorder. We present a 3-year-old girl with BS type 4 and sensorineural hearing loss who received cochlear implantation (CI) after failing a hearing screening. The patient had a successful left-side implantation but later developed a flap infection, initially treated with antibiotics and surgical repair using a vascularized flap, which failed. During the same repair procedure, the right ear was implanted successfully. A third surgery was required to remove the left implant and close the wound with a temporoparietal flap, performed by plastic surgery. This is the earliest report on managing device extrusion in BS. The literature review highlights that the outcomes of CI in patients with BS vary significantly within each syndrome group and that the presence of additional disabilities accentuates this diversity. Our case illustrates that CI can improve the quality of life for patients with BS, but a multidisciplinary team is crucial for managing these cases. We stress the need for further studies to evaluate realistic outcomes and complication rates, as this will guide future treatment strategies.

Introduction

Hearing loss is a common congenital disability in developed countries, with an incidence of 2 to 3 per every 1000 infants. ¹ It is classified into three types: conductive, sensorineural, and mixed. ² Hearing loss may result from various factors, including genetic predispositions, acquired conditions, or idiopathic causes. Genetic factors account for over 50% of cases ³ ; approximately 30% are associated with additional abnormalities and are therefore classified as “syndromic.” ⁴ Sensorineural hearing loss is found in many syndromes, including Pendred syndrome, Alport syndrome, Jervell and Lange-Nielsen syndrome, Usher syndrome, Waardenburg syndrome, and Bartter syndrome (BS) type IV.^5,6 Diagnosing these syndromes is challenging in patients with mild symptoms, and identifying the underlying cause is often more crucial, as the accompanying clinical symptoms may be more severe.

Bartter syndrome is an autosomal recessive disease. It was first described in 1962 as hyperplasia and hypertrophy of the juxtaglomerular apparatus, along with primary aldosteronism and hypokalemic alkalosis. ⁷ It is defined by renal salt-wasting, hypokalemic metabolic alkalosis, and elevated renin and aldosterone levels. ⁸ Earlier studies have attributed BS to deficient chloride reabsorption in the distal nephron, ⁹ and mutations in five genes,^10,11 as summarized in Table 1.

Table 1.

Genetics of Bartter syndrome and typical clinical findings.

	Gene	OMIM	Inheritance	Protein	Clinical findings
Type I	SLC12A1	601678	AR	NKCC2	Prematurity, polyhydramnios, nephrocalcinosis, hypokalemic alkalosis, hyposthenuria
Type II	KCNJ1	241200	AR	ROMK1	Prematurity, polyhydramnios, nephrocalcinosis, hypokalemic alkalosis, hyposthenuria, transient hyperkalemia
Type III	CLCNKB	607364	AR	CLC-Kb	Hypokalemia, hypochloremic alkalosis
Type IVa	BSND	602522	AR	Barttin	Prematurity, polyhydramnios, sensorial deafness, hypokalemia, hypochloremic alkalosis
Type IVb	CLCNKA CLCNKB	613090	AR	CLC-Ka CLC-Kb	Prematurity, polyhydramnios, sensorial deafness, hypokalemia, hypochloremic alkalosis
Transient BS	MAGE-D2	300971	XLR	MAGE-D2	Transient salt wasting, polyhydramnios
AD hypocalcemic hypercalciuria	CASR	601198	AD	CaSR	Hypocalcemic hypercalciuria

In 1995, a new variant of BS called the infantile variant, which presents with sensorineural deafness, was reported. ¹²

Infantile BS is caused by autosomal recessive mutations in the BSND gene, located on chromosome 1p31, which encodes the Barttin protein.^13,14 Barttin protein is an essential subunit of the ClC-Ka and ClC-Kb chloride channels, located in the renal tubules of the loop of Henle, distal convoluted tubule, and cortical collecting ducts. It is also present in the potassium-secreting epithelial cells located in the inner ear. ¹⁵ In BS type IVa, mutations in the BSND gene impair potassium secretion in the stria vascularis and vestibular labyrinth, leading to sensorineural hearing loss. In BS type IVb, mutations in both CLCNKA and CLCNKB genes affect chloride channels, further disrupting inner ear function. Previous studies indicated that sensorineural deafness in infantile BS occurs due to the loss of outer hair cells and a decrease in the mechanoelectrical transduction current of inner hair cells, resulting from a decline in the endocochlear potential. ¹⁶ The fundamental mechanisms of salt-losing renal tubular disorders have attracted the scientific community's interest as a potential cause of associated deafness.

Cochlear implantation (CI) is a treatment for patients with profound bilateral sensorineural hearing loss who receive no benefit from hearing aids (HAs). ¹⁷ CI directly stimulates the auditory nerve, circumventing injured hair cells of the cochlea and providing salient coded information to enhance speech perception. ¹⁸ The literature on performing CI in patient with BS with hearing loss is lacking. In this report, we assess the use of CI in infantile BS, highlighting the concerns and consequent complications surrounding CI. These include the tendency for wound infection, healing process issues up to device extrusion, and our experience in dealing with and managing these complications. We also provide a comprehensive review of the literature on similar cases.

Case presentation

A 3-year-old girl of Caucasian ethnicity was referred to our ear specialist center with profound bilateral sensorineural hearing loss since birth, confirmed by auditory brainstem responses (ABRs). Neonatal screening data showed that the child failed otoacoustic emissions (OAEs) screening three consecutive times. ABR testing confirmed profound bilateral hearing loss with the instability of the Wave V threshold.

The girl was born prematurely at 32 weeks of gestation via cesarean section due to polyhydramnios. Her birth weight was 1.6 kg. Cytomegalovirus testing was negative, and there was no history of maternal TORCH infections. She presented with renal salt-wasting, hypokalemic metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism and had multiple hospital admissions due to electrolyte imbalances. Despite these complications, she had no vestibular complaints and no family history of hearing loss.

Due to prematurity and failure to thrive, the infant required nasogastric feeding for adequate nutritional support. As a result, a gastrostomy tube was placed to ensure sufficient nutrition and electrolyte supplementation.

The preoperative work-up included an electrolyte assessment by the pediatric nephrology team, audiological evaluations, imaging studies, and speech and psychological testing.

Audiological tests included OAEs to assess outer hair cell function, which was absent, indicating outer hair cell function. Tympanometry was performed to evaluate middle ear function, and a bilateral type A tympanogram was shown, suggesting normal middle ear pressure and compliance. ABRs were conducted to assess the auditory pathway from the cochlea to the brainstem. The results showed no identifiable ABR waves at high-intensity levels (100 dB HL) in the 2 to 4 kHz region, confirming bilateral profound sensorineural hearing loss.

Imaging studies comprised computed tomography (CT) and magnetic resonance imaging (MRI) of the temporal bones to assess cochlear structure and confirm the presence of cochlear nerves. The results showed a normal, well-aerated mastoid, cochlea, and facial nerve with intact bilateral cochlear nerves. No cochlear nerve deficiency was observed on axial or coronal views of the temporal bone, as shown in Figure 1.

Figure 1.

An illustration of the MRI T2 findings showing patency of cochlea on both sides coronal view (a), presence of facial and cochlear nerve—coronal view (b), sagittal oblique view MRI shows the presence of facial nerve and cochlear nerve right side (c) and, left side (d). MRI: magnetic resonance imaging.

Speech and psychological assessments were also conducted, confirming that the child had a normal IQ. Despite using bilateral hearing aids for 1 year, no auditory benefit was observed. Based on these findings, the cochlear implantation (CI) committee recommended CI surgery, and after obtaining parental consent, the child underwent CI implantation at the age of 13 months.

Anesthesia challenges included close intraoperative monitoring of electrolyte imbalances (especially potassium, magnesium, and calcium) with necessary corrections, fluid management to prevent dehydration and electrolyte shifts, ensuring renal and liver function stability, maintaining cardiovascular stability, and cautious use of muscle relaxants to avoid hyperkalemia. Postoperative pediatric intensive care unit (PICU) monitoring was required.

The surgical procedure was performed by an experienced otolaryngologist, with facial nerve monitoring to prevent injury. Electrocochleography was used to monitor cochlear function, ensuring optimal auditory nerve stimulation. Intraoperative imaging confirmed accurate electrode placement inside the cochlea. The procedure involved full electrode insertion via posterior tympanotomy with round window electrode placement. A MED-EL Synchrony Form 24 implant was placed in the right ear, while an MED-EL Synchrony 2 Flex 26 implant was used for the left ear. The patient was fitted with a Sonnet 2 processor with a DL Coil. The postoperative period was uneventful, with no immediate complications observed. Electrically evoked compound action potential (ECAP) and impedance measurements were within normal limits, confirming proper device function and neural responsiveness.

After 3 months, the patient started to have wound infection flap dehiscing and device extrusion. Frequent wound care and IV Ceftriaxone antibiotics were initiated, and simple closure was done without benefits after 1 month. Therefore, the CI committee decided to go for right-side CI and left a partial-temporal flap for closure on the left side done by a plastic surgeon. After the surgery, her condition extraordinarily improved the next year (Figure 2), and she followed the aural rehabilitation program. After implantation, her audiometric thresholds improved to 35 dB and progressed to 25 dB. Furthermore, the latest results of the Speech, Spatial, and Qualities of Hearing Scale showed good outcomes, with average scores of 7.3/10 for speech, 7.6/10 for spatial, and 8.6/10 for the qualities subscales. The Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scores also demonstrated significant improvements. Preoperatively, the child had a CAP score of 0, indicating no awareness of environmental sounds or voice, and a SIR score of 1, meaning connected speech was unintelligible. Postoperatively, the CAP score improved to 4, reflecting the ability to understand common phrases without lip-reading, while the SIR score increased to 3, indicating that connected speech became intelligible to a listener who concentrates and lip-reads.

Figure 2.

The wound condition after the plastic surgery.

Discussion

Bartter syndrome is diagnosed based on history, physical examination, specific laboratory findings, and genetic testing. Several gene mutations were reported to cause BS, such as BSND, SLC12A1, CASR, KCNJ1, CLCNKA, and CLCNKB.^19,20 BSND mutations cause BS type 4a, while CLCNKA and CLCNKB mutations were reported to cause BS type 4b combined with sensorineural deafness. Several diseases cause mutations in the BSND gene, impacting the function of ClC-K channels, such as R8L, R8W, G10S, Q32X, G47R, and G10S. Even though the R8L, R8W, and G10S mutations impair the function of ClC-K channels, no effect on the insertion of the channel-to-surface membrane has been detected. ²¹ Contrarily, G47R mutation affects the renal phenotype as the binding of mutant batting to ClC-K channels is less effective.^22,23

Role of cochlear implantation

Numerous reports exist on applying CIs in many syndromes with variable outcomes. Broomfield et al. ⁵ included five cases, one case each of Stickler syndrome, Bartter syndrome, Down syndrome, CINCA syndrome, and Donnai–Barrow syndrome. Two patients reached a Speech Reception Score (SRS; 0: no speech perception, 6: open set recognition of words) of four, while the other three achieved a full score of 6. Also, a retrospective study included four girls and two boys with infantile BS combined with sensorineural hearing loss. All cases had a history of previous hospital admissions due to renal impairment. Five children were treated with CI, which improved speech perception and development. However, exceptional hearing performance was not realized due to late treatment and associated comorbidities. ²⁴

When accounting for children with a syndromic etiology for their hearing loss, it is evident that there is often broad variation within each syndrome group. Previous reports of CI in children with additional handicaps emphasize this range of outcomes, with those having neurological or developmental abnormalities often scoring the lowest on traditional tests of speech and language development.^25–28 In these children, higher cognitive function appears to be the key predictor of outcomes and may, therefore, be more suitable for pre-operative implant assessment than the underlying etiology itself.^25,26 Unfortunately, measuring cognitive function is challenging and may necessitate the involvement of specialists experienced in developmental evaluations for hearing-impaired children. ²⁹ In addition, global developmental assessment is a crucial component to consider both throughout the candidacy process and after CI, along with the improvement of delayed-developing children ³⁰ . Visual impairment is also a risk factor that should be considered in children who undergo CI.^31,32 It is fascinating to note that a diagnosis of cognitive impairment may not be made before CI and only discovered after the surgery. Rehabilitation should focus on strengthening the ability of these cases to attach meaning to the environmental sounds and guiding parents on using strategies to develop those skills. That is why studies of cases with other disabilities often experience improved quality of life after cochlear implantation despite poor speech and language results.^30,33 Therefore, traditional speech perception measures are not enough to assess the benefit to a child; different assessment tools measuring CI's educational, social, and psychological outcomes are required. Unfortunately, such benefits are difficult to determine and quantify.^34,35

Complications of CI

Young children aged 1 to 2 years encountered more infectious complications than older children. ³⁶ However, the advantages of early implantation for language progress are well recognized, and the low absolute risk of infection does not outweigh these considerable advantages. ³⁷

CIs are a relatively safe and effective option for managing severe to profound sensorineural hearing loss associated with a low incidence of postoperative complications.^38,39 Those complications are often classified as minor and major complications, ⁴⁰ with insignificant complications that can be treated by conservative measures and some relieved by switching off electrodes. They include transient facial palsy, tinnitus, subperiosteal hematoma, pain, and infections not requiring surgery. On the other hand, significant complications usually require surgical intervention, such as meningitis, cerebrospinal fluid otorrhea, severe infection with tympanic membrane perforation, and cholesteatoma. ⁴¹

The most contributing factors to the overall rise in infectious complications were frequent and usually early problems. These complications include skin flap necrosis, dehiscence, infection, and device extrusion, which approximately occurred in 1.7% to 10% of cases.^42,43 The resultant defects often necessitate providing healthy, vascularized soft tissue to cover the implant. ⁴⁴

We review some of the more extensive studies in the literature to provide insight into those complications’ incidence. A retrospective study showed that among 1500 CI, 20 patients experienced hematoma, and 15 experienced seroma around implants. Ten patients recovered in 2 weeks through applying adequate drainage, antibiotics, and pressure dressing. However, five patients were complicated with flap necrosis and underwent contralateral reimplantation. Four patients experienced abscesses around implants; two of those recovered within 2 weeks of applying drainage, antibiotics, and gentamicin irrigation. The other two developed flap necrosis and received contralateral reimplantation. ⁴¹ Another retrospective study included 811 children with CI; 12 of those developed skin flap complications. Seven children received conservative treatment, while five underwent revision surgery, resulting in wound closure for three and an explanation for two. ⁴⁵ Immunocompromised patients with organ transplants face challenges after CI. A retrospective study showed that organ transplant recipients, particularly children, had a higher rate of postoperative complications compared to healthy individuals. ⁴⁶

Cochlear implant extrusion is a prevalent complication after CIs. ⁴⁷ A study on cochlear implant extrusion through the skin of a young girl reported that it appeared to be due to pressure necrosis from the implant on the overlying tissues. The authors believed that it could be reduced by angulation of the CIs prior to insertion so that it adapts to the curvature of the skull, thus reducing pressure on the tissues. ⁴⁸ CI extrusion is usually managed by culturing the wound, prescribing an appropriate antibiotic, debridement, or simple closure covering with a local flap Unless the wound is too big or the patient develops additional soft tissue issues (e.g. flap hypervascularity or pressure necrosis by the device), the patient will often receive a local or regional flap. As a result, only a few instances of free flaps are successfully used to deal with CI extrusion.^44,45 Most cases succeeded in using variable regional flaps.^{44,45,47–49} Carnevale and colleagues recommended that in extrusion cases with hypovascularization of the postauricular region, using an inferiorly based fascia-muscular flap instead of the usual anteriorly based flap should provide better results. ⁴⁶ Gawcki et al. ⁵⁰ reported that two-layer coverage comprised of an inner temporalis muscle fascia flap and an outside rotation skin flap successfully covered 52.6% of their exposed and contaminated CIs. They concluded their sequence of single-layer closures with rotation skin flaps was unsuccessful. However, because of its size and more anteriorly located vascular pedicle, the temporalis muscle flap is constrained in its range of motion and malleability. There are case reports of temporoparietal fascial flaps successfully covering CIs. ⁵¹ The temparo-parietal flap has a dense vascular plexus, is flexible, and has a considerably wider reach than the temporalis muscle flap. ⁵² As a result, it becomes the ideal flap for covering implants. In addition, the receiver should be positioned at least 1.5 cm from the edge of the wound. A U-shaped postauricular incision should be utilized, and flap thinning should stop at the level of the hair follicles. Patients should be given perioperative antibiotics as a preventive precaution, and in cases with significant medical comorbidities, long-term antibiotics should be considered. ⁵³ There is a gap between rigorous studies examining the impact of patient-level variables on wound complications and routinely reporting wound problems in CI research. ⁵⁴

Nutritional status, hearing loss, and wound healing

Additionally, previous studies indicated that various nutritional factors could affect wound healing. Deficiencies in vitamins A, C, and E, as well as zinc and iron, have resulted in poorer healing conditions due to increased vulnerability to infection.^55,56 Also, large amounts of protein can be continuously lost through wound exudates due to an operation, which may raise the metabolic demands of the wound region. ⁵⁷ Consequently, guidelines for preserving a proper nutritional status are needed to avoid some of the causes and burdens of wound healing. ⁵⁸

Conclusion

As specific genetic syndromes can result in life-threatening abnormalities, timely diagnosis, and intervention are essential. Major complications post-CI require careful monitoring and informed decision making by experts. A multidisciplinary evaluation by pediatricians, nephrologists, otolaryngologists, and audiologists is often necessary to successfully navigate those cases. The reporting of this study conforms to CARE guidelines. ⁵⁹