Protocol for Evaluation and Management of Hearing Loss After Meningitis

Abstract

Bacterial meningitis is the most common cause of post-natal acquired hearing loss in children. Although cochlear implantation helps in improving the hearing in these patients, the fibrosis and ossification of the cochlear lumen that occurs as a result of bacterial meningitis, limits the chances of successful implantation. In developing countries like India, the reduced awareness, limited resources, and financial constraints warrant judicial use of radiological and audiological tests to increase the rate of successful cochlear implantation. The present paper is a review of the literature and a proposed protocol for follow-up of post-meningitis patients to help clinicians diagnose and hence, intervene early when profound hearing loss occurs. Every patient who has had an episode of bacterial meningitis must be followed up for atleast 2 years for possible hearing loss with frequent audiological and radiological evaluation, as required. Cochlear implantation must be done as early as possible when profound hearing loss is detected.

Introduction

Bacterial meningitis is a major cause of morbidity in children under 5 years of age, especially in countries where vaccination for H. influenzae type b, S. pneumoniae and N. meningitidis is not a part of the national immunization programs yet. It is the most common cause of post-natal hearing loss in children. Five to ten percentage of patients with bacterial meningitis develop permanent bilateral profound hearing loss affecting the quality of life significantly. Streptococcus pneumoniae and Neisseria meningitidis are the most common organisms causing meningitis. However, the incidence of hearing loss is much higher in patients with S. pneumoniae meningitis than with N. meningitidis [1, 2, 3, 4].

The hearing loss in many of these patients remains undetected, especially in young children, where hearing loss is discovered only when a formal assessment is done. Other reasons for the delay in detection are the prolonged duration of the morbidity as well as the neurological consequences of the disease itself, like communication difficulty and varying degrees of aphasia. The longer the period of auditory deprivation, the greater the consequences [5]. Especially in pre-lingual children, this can have a devastating effect on speech and cognitive development [6].

Cochlear implant is the treatment of choice for profound hearing loss. In post-meningitic hearing loss, though the results are fairly good, several factors determine the success of the implant, patency of the cochlear lumen being the most important [5, 7, 8].

Pathophysiology of Hearing Loss Post-meningitis

Studies suggest that inflammatory labyrinthitis develops from the spread of infection into the inner ear via the cochlear aqueduct. The cochlear aqueduct drains into the scala tympani adjacent to the round window; hence the initial concentration of inflammatory mediators occurs in this region which explains the predominant degree of injury in this area [9]. The labyrinthitis progresses through the stages of acute purulence followed by serofibrinous exudate and fibrosis in the perilymphatic spaces and finally ossification. The fibrosis can begin as early as 3 days after the onset of infection and the ossification process can progress for up to a year [10–12]. Because of this progressive obliteration of the cochlear lumen, the implantation can become increasingly difficult within a few weeks, and hence periodic follow-up and early intervention are warranted.

India is a country with a large and diverse population and limited resources. Affordable and cost-effective health care facilities are not available in all parts of the country. To optimally use the available facilities without compromising the quality of treatment provided to the patients, a protocol for hearing evaluation and follow-up after bacterial meningitis is hereby proposed.

Materialand Methods

A comprehensive electronic literature search was conducted by the two authors separately, looking for published articles using the keywords ‘bacterial meningitis’, ‘hearing loss’, ‘hearing evaluation’, ‘labyrinthitis ossificans’, and ‘Magnetic Resonance Imaging (MRI)’. The medical databases used in the literature search were PubMed, MEDLINE, the Cochrane Library, Index Copernicus and Scopus. In addition to the collected articles, their reference lists were also checked for eligible studies. The various articles were reviewed systematically. The following clinical information was compiled: (1) Incidence of hearing loss in patients of bacterial meningitis. (2) Onset and progression of hearing loss. (3) Protocol followed for hearing evaluation. (4) Protocol followed for radiological investigation. A protocol was devised based on the recommendations of the various international authors and modified to suit the context of a developing nation such as India.

Discussion

Initial Treatment: Dexamethasone

Bactericidal antibiotics used in the treatment of bacterial meningitis promote the release of bacterial cell wall products such as endotoxins which provoke the production of inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), and platelet-activating factor (PAF). These inflammatory changes lead to nerve damage and deafness. Steroids have anti-inflammatory effects and decrease the release of various cytokines, which reduces the production of inflammatory mediators [13, 14].  Hence, it is recommended that steroids be given before the first dose of the antibiotic [15]. Dexamethasone is recommended in the dose of 0.6 mg/kg/day divided into 4 doses given for 2–4 days [16]. A Cochrane Database Systemic Review published in the year 2015 found that corticosteroids reduced the incidence of severe hearing loss and any hearing loss in patients with acute bacterial meningitis. Dexamethasone was found to be the corticosteroid of choice as it has superior Cerebro-Spinal-Fluid (CSF) penetration and a longer half-life. Though the timing of the corticosteroid (before, with or after the first dose of antibiotic) did not show any significant difference in sequelae, it was recommended that the corticosteroid be given before or with the first dose of antibiotic [15]. Another study by Fox JL (2006) reconfirmed the benefit of dexamethasone [17]. However, limited benefits were found in the ‘Third World Countries’ and this was attributed to the delay in presentation to the clinician and the use of inappropriate anti-bacterial therapy. It was recommended that steroids should not be given in patients presenting with late-stage meningitis and in those with septic shock. The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) in its guidelines published in 2016 supports the use of Dexamethasone in the dosage of 0.15 mg/kg given every 6h for 4 days, to be started before or with the first dose of antibiotics to prevent severe neurological sequelae including hearing loss [18].

Imaging

The imaging protocol for post-meningitis hearing evaluation includes a high-resolution Gadolinium-enhanced Magnetic Resonance Imaging (MRI) and a High-Resolution Computed Tomography (HRCT) of the temporal bones. MRI protocol for post-meningitis imaging followed at our institute includes multiplanar T1-weighted, T2-weighted, T2-DRIVE, post-gadolinium T1-weighted and post-gadolinium T2 FLAIR sequences. MRI is believed to be superior to HRCT in demonstrating early signs of fibrosis in the cochlea [19, 20]. Abnormal low T2 signal (loss of fluid signal) within the scala tympani and vestibuli of the cochlea are the earliest findings suggestive of the beginning of fibrosis. Gadolinium-enhanced MRI (GdMRI) has the ability to establish the presence of active labyrinthitis as it detects the increased blood supply to the striae vascularis which is indicative of active inflammation [21]. Gadolinium enhancement may be required only during the acute phase of the disease, as non-contrast T2-weighted images are sensitive enough to pick up loss of fluid signal and hence can establish the presence of fibrosis in the cochlea. MRI has high sensitivity and positive predictive value in identifying labyrinthitis ossificans but the negative predictive value and specificity are low [20].

Van Loon et al. retrospectively studied the MRI scans of 17 patients with confirmed bacterial meningitis and correlated them with the occurrence of hearing loss and per-operative findings during CI surgery [22]. Cochlear enhancement in GdMRI was found in 87% of the ears with Sensorineural Hearing Loss (SNHL). In all cases of incomplete electrode insertion during CI, loss of cochlear patency was already seen on T2-weighted MRI (high sensitivity). However, a loss of fluid was also seen in 29% of the cases in which a full electrode insertion was achieved (low negative predictive value).

Kopelovich et al. studied 23 children who survived bacterial meningitis to correlate the findings of GdMRI done during acute disease with the development of hearing loss [23]. GdMRI was found to be 87% sensitive and 100% specific for predicting which ears would develop permanent SNHL. Labyrinthine enhancement was detected as early as 1 day after diagnosis. Another study by Orman et al demonstrated high specificity and average sensitivity of T1-weighted GdMRI for the prediction of SNHL in infants with bacterial meningitis [24].

A multicentre study published in 2009 compared the T1 and T2 weighted MRI scans of the labyrinth of 45 patients who suffered from meningitis-induced hearing loss with surgical findings during cochlear implantation [21]. A slightly higher percentage of agreement with surgery was found for T2-weighted MRI than for T1-weighted MRI but the difference was not found to be significant.

HRCT of the temporal bones must be done prior to surgery as it is an anatomical road map. The presence of ossification on HRCT has a very high positive predictive value but is often a late sign and is suggestive of severe stages of ossification.

Based on HRCT findings, Balkany et al. [25] graded the degree of ossification from 0 to 3 as:

Grade 0: Normal cochlea without any ossification

Grade 1: Ossification affects only the basal turn of the cochlea

Grade 2: Ossification affects two turns of the cochlea

Grade 3: Ossification affects three turns of the cochlea

The information about the degree of ossification is very important in planning the timing and the procedure of the surgery. In the early stages, simple manipulation of the soft tissues or minor drilling into the scala tympani of the basal turn might be enough for the complete insertion of the electrode. In later stages, a different choice of procedure may be required like scala vestibuli insertion, middle turn cochleostomy with anterograde/retrograde middle turn insertion or even a double array insertion after middle and basal turn cochleostomy. Aschendorff et al reported the case of a five-month-old baby who had to undergo bilateral CI urgently as the HRCT was suggestive of significant ossification of both cochleae just one-month post-meningitis [26]. Scala vestibuli insertion was done as no lumen could be found in scala tympani. However, a complete insertion was achieved.

Ideally, the cochlear implantation must be done urgently as soon as any signs of fibrosis are observed radiologically. In cases when the cochlear implantation is being deferred due to a lack of financial resources, one may even consider stenting of the cochlea to prevent further obliteration of the lumen and an active implant can be inserted as and when feasible [27].

The depth of insertion of the active electrode into the cochlea is highly related to the degree of hearing improvement. Several studies have demonstrated better audiological outcomes in patients with complete electrode insertion when compared to those with partial electrode insertions [5, 7]. Hence, early detection of the ossification process is extremely important in ensuring good results post-implantation.

Hearing Evaluation

The hearing loss after meningitis can occur as early as a few days to as late as even one-year post-infection. A study conducted in the Netherlands showed the incidence of hearing loss to be nearly 28% with 18% incidence of profound hearing loss. Several patients showed deterioration of hearing loss with time while a few had fluctuating hearing loss [2]. Another study in Kenya found at least unilateral mild hearing loss in 44.4% of the children treated for meningitis, with 17% incidence of severe to profound hearing loss [28].

Several studies have delineated the importance of periodic audiological evaluation of all patients after bacterial meningitis. Brookhouser et al. published a study in 1988 where they followed 64 children with hearing loss after an episode of bacterial meningitis for an average of 3.46 years [29]. Fifty five (86%) of these had stable auditory thresholds over time. 9 (14%) had variable auditory thresholds, including 4 children who had improving auditory thresholds, 3 with declining thresholds, and 2 who had fluctuating thresholds over a variable interval, ranging from 1 month to 12 years. It was suggested that a hearing evaluation be done as soon as feasible as the hearing loss could occur as early as during the phase of bacteremia. If no hearing loss was detected in the first evaluation, a re-evaluation would be done after 6 months. If hearing loss was detected, audiological revaluation would be done every three months until the thresholds were stable. Once thresholds were stable, revaluation would be done at least annually to implement needed rehabilitation on a timely basis.

A group of researchers in France retrospectively studied five patients who developed hearing loss after an episode of meningitis and found that the range of days taken between diagnosis of meningitis and severe hearing loss varied between 9 and 210 days. They recommended that age-appropriate audiological evaluation must be done every 4 months for 2 years after meningitis [30]. The Dutch Cochlear Implant Group recommends audiological follow-up at 1, 2, 6, and 12 months after first evaluation when the hearing in the first evaluation was found to be normal [2, 16].

However, the situation is very different in developing countries owing to the limited resources as well as the lack of trained professionals in the peripheral parts of the country. A study in South Africa found that only 60% of the patients with bacterial meningitis were referred to appropriate professionals for audiological assessment [31]. Even among the patients referred, most patients underwent only otoscopy and tympanometry. Only about 32% of the patients underwent Oto-Acoustic Emissions (OAE), none of the patients had even a basic Pure Tone Audiometry (PTA) or Brainstem Electrically-Evoked Response Audiometry (BERA). The majority of the referrals were made during the hospital stay, with hardly any referrals after three months post-discharge from the hospital. Considering the possible fluctuation or deterioration of hearing for several months post-meningitis, several patients with hearing loss were probably missed. The need for an appropriate protocol for hearing evaluation that could be used by clinicians of all specialties and other allied healthcare professionals was highlighted.

Wilson et al. demonstrated the improvement in audiological testing in children post-meningitis over three audit cycles (1994–2001) with appropriate interventions including better communication between the referring paediatrician and other specialties involved, better education of the nursing staff in the intensive care units, information leaflets distributed to families and an updated referral pathway taught to all members of the treating team [32]. Hence the need for a protocol was felt which could be used by all clinicians involved in the management of meningitis. This would ensure timely referral of patients to the audiologist/ cochlear implant surgeons, when required.

In recent years, governments in many developing nations, like India, are trying to provide funds for the management of individuals with hearing loss. However, most of these programs cover only the cost involved in the surgery and rehabilitation post-surgery. Very few programs provide the funds for the investigations, including radiological evaluation, required for making the appropriate diagnosis. Significant time is lost between the suspicion of the presence of hearing loss and the diagnosis of labyrinthitis ossificans. With an appropriate protocol in place, resources could be used judiciously, ensuring quick diagnosis and intervention.

Protocol (Figure 1)

Figure 1.

Protocol for evaluation and management of hearing loss after meningitis

The first hearing evaluation should be done as soon as possible in every patient with confirmed bacterial meningitis. An initial test in the form of OAE can be done while the patient is still in the hospital. In case of the absence of OAEs, the patient must be referred to a cochlear implant centre for objective and quantitative evaluation as soon as possible.

Depending on the findings of the initial Magnetic Resonance Imaging (MRI) scan, if there are signs of active enhancement in the membranous labyrinth, suggestive of early fibrosis, a detailed hearing evaluation, including subjective and objective tests such as PTA and BERA, should be done as soon as possible after discharge and the patient must be referred to a cochlear implant centre as soon as feasible. If the initial scan showed no signs of fibrosis (loss of fluid signal on T2-weighted images) in the cochlea, the hearing evaluation must be done within 6 weeks. If hearing loss (mild to severe/profound) is found, the patient must be observed for progressive or persistent hearing loss with a hearing evaluation performed every 6 weeks up to 2 years. MRI (Non-contrast, T1 and T2 weighted sequences) must be done at the first sign of progression of hearing loss and if any signs of fibrosis are seen on MRI, cochlear implantation must be considered. If there are no signs of fibrosis, the MRI must be repeated every 3 months for up to 2 years after the meningitis episode.

If no hearing loss is found at the first hearing evaluation, tests must be repeated every 3 months and MRI must be done if any progression of hearing loss is observed. In patients with irreversible and non-progressive minimal/mild/moderate/moderately-severe hearing loss, appropriate hearing rehabilitation must be done with hearing aids. Every patient must be followed-up for at least 2 years after meningitis.

Conclusion

Hearing loss post meningitis can have a significant effect on the quality of life of the patients and hence hearing rehabilitation must be done as soon as possible. To ensure these patients are evaluated appropriately and referred to a designated cochlear implant centre for management at the earliest, we propose this protocol which can be used by all clinicians treating patients with bacterial meningitis.

Funding

No source of funding to be declared.

Declarations

Conflict of interest

No conflict of interest to be declared.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.