Sensorineural Hearing Loss Following Acute Bacterial Meningitis in Non-neonates B. Cherian, T. S i n g h , B. Chacko and A. Abraham 1
Departments of Pediatrics, INenrology, Christian Medical College, Ludhiana, Punjab, India. Abstract, Objective : Sensorineural hearing loss (SNHL) is an important sequelae of acute bacterial meningitis (ABM) in children. This study was undertaken to determine the incidence of SNHL following meningitis in non-neonates and its correlation with various factors. Methods : Children between the ages of 1 month and 12 years with ABM admitted in a teaching hospital over a period of 18 months were enrolled. Detailed history was taken, clinical examination performed and cerebrospinal fluid analyzed at commencement of therapy, 48 hours later and at the end of treatment. On discharge brainstem evoked response audiometry (BERA) was recorded. Data were analyzed using appropriate statistical tests. Results : Out of 32 children enrolled, 9 (28.1%) developed SNHL, bilateral in 21.9% and unilateral in 6.2%. Among hearing impaired subjects, 11.2% had mild while 44.4% each had moderate and profound hearing loss. Age, presence of vomiting, altered sensorium seizures and aminoglycoside usage were not significantly different in those with and without SNHL, but the total duration of fever was (p <0.05). There was significantly higher protein content and neutrophils in the second CSF sample of those with SNHL. Conclusion : There is a greater than 50% probability of the child developing SNHL if neutrophil percentage in the second CSF is 80% or more. Since the overall risk of SNHL is significant in children with meningitis, it is recommended that BERA be recorded in all, so that early intervention may be possible. [Indian J Pedlatr 2002; 69; (11) : 951-955] K e y words :
Meningitis; Hearing loss; Non-neonates
Hearing loss in very early life can affect the development of speech and language, social and emotional development and academic achievement of the young child. 1The hearing impaired has a multitude of learning problems due to impaired language acquisition, communication skills and social adjustment. Acute bacterial meningitis accounts for 90% of all causes of acquired hearing impairment by the age of 3 years. 2 Damodaran et al observed an incidence of unilateral SNHL following meningitis in 14% and bilateral in 11.9% 3, while Aneja and Aggarwal reported the same in 10% and 12.5% respectively? There appears to be a large number of risk factors which could be used to predict hearing loss following me"run~tis. This prospective study was conducted to determine the incidence of SNHL following ABM in non-neonates and also to determine the correlation, if any, with various factors throughout the clinical course of the illness. MATERIALS AND METHODS
All children between the ages of I month and 12 years who were diagnosed to have ABM and admitted to the pediatric ward of Christian Medical College and Hospital were enrolled in the study. Children with birth asphyxia, Reprint requests : Dr. BettyChacko, Reader, Deptt. of Pediatrics, ChristianMedicalCollege,Ludhiana,Punjab- 141 008. E-mail : bettychacko@hotmaiLcom Indian Journal of Pediatrics, Volume 69--November, 2002
neonatal hyperbilirubinemia, neurodevelopmental delay, prior hearing impairment and family history of deafness were excluded from the study. All patients had detailed history and clinical examination. Cerebrospinal fluid was analyzed at admission, 48 hours later and at the end of treatment by direct microscopy, biochemical tests, gram stain and culture. All cases were treated by the respective clinicians based on the clinical status and microbiological profile. On admission, the drugs of choice were penicillin and chloramphenicol, unless the infant was very young or septicemic. In the latter case a 3 rd generation cephalosporin in combination with an aminoglycoside was administered. The drugs were changed or an additional one added only if the 2~d CSF examination showed no improvement. Corticosteroids were administered to none of the patients. Daily follow-up of patients was done and clinical complications were noted. On discharge, which coincided with the completion of therapy, varying from 10 to 51 days, Brainstem Auditory Evoked Response (BAER) was recorded. Evoked Response A u d i o m e t r y was done by recording the responses for each ear for a range of sound intensities from 30 to 105 decibels. At each of these decibels 7 wave forms are produced. The presence of Wave-5 which is the most consistent one, implies normal hearing for the particular decibel of sound. BERA was performed as far as possible in the natural sleep. The hearing impaired children were classified by the Davis and Silverman 951
B. Cherian et al
hearing Classification. 5 Estimated hearing level for speech (dB) <40 40-55 55-70 70-90 >90
Hearing Class Normal Mild Moderate loss Severe loss Profound loss
lasted for longer time in the hearing impaired group, this difference too was not statistically significant. But the total febrile d a y s w e r e s i g n i f i c a n t l y m o r e in the h e a r i n g impaired group. Figure I shows the neurological signs and complications encountered in the patients. There was o n l y one child w i t h s u b d u r a l e f f u s i o n a n d he h a d developed profound SNHL.
For purposes of analyses the patients were divided into 2 groups - Group I with normal hearing and Group II with s e n s o r i n e u r a l h e a r i n g loss. The g r o u p c o m p a r i s o n s involving quantitative variables were a n a l y z e d using student's 't' or Mann-Whitney 'U' statistics. Comparisons of qualitative variables were carried out using Chi-square test or Fisher's exact test as applicable. RESULTS P value > 0.5 for all parameters
Out of thirty two children who were enrolled, 50% were infants and 75% were males. Hearing loss was recorded in 9 cases (28.1%), unilateral in 2 (6.2%) and bilateral in 7 (21.9%). SNHL was observed in 29.1% males and 25% females (p>0.05). A m o n g the nine h e a r i n g i m p a i r e d percent four children each had m o d e r a t e or p r o f o u n d SNHL (Table 1). Fifty percent of infants between the ages of one to three months developed SNHL. There was an increasing incidence of hearing loss with decreasing age but this trend was not statistically significant nor was the the severity of hearing loss in the various age groups. (Table 2) TABLE 1, Hearing Loss
Hearing loss
Number of cases
Percentage
Mild (30 - 55 dB) Moderate (55 - 70 dB) Severe (70 - 90 dB) Profound (> 90 dB) Total
1 4 0 4 9
3.1 12.5 0 12.5 28.1
TABLE2. A g e Distribution & Severity of Hearing loss
Age (months)
Total No.
Mild SNHL
Moderate Profound Total SNHL SNHL SNHL
1- 3
8
0
2
2
4 (50%)
3- 12 12 - 24 24 - 60 > 60 Total
8 3 6. 7 32
0 0 0 1 1
1 1 0 0 4
1 0 1 0 4
2 (25%) 1 (33.3%) 1 (16.7%) 1 (14.3%) 9 (27.9%)
p value =0.61 The clinical correlates in Groups I and II are given in Table 3. The age, mean duration of fever, vomiting and headache revealed no significant difference between the two groups. Although seizures were more frequent and 952
Fig.
1. Neurological Signs and Complications
The mean total leukocyte count between the normal a n d i m p a i r e d g r o u p d i d not c o r r e l a t e w i t h S N H L . However, when leucocytosis (TLC > 11000/cumin) was c o m p a r e d the difference was f o u n d to be significant. (Fisher's exact p v a l u e = 0.04). The CSF culture w a s positive in 6 patients (18.7%). Neisseria meningitidis was cultured in 3 , p n e u m o c o c c u s in I and staphylococcus aureus in 2 cases. The only patient with pneumococcal meningitis h a d p r o f o u n d deafness. One p a t i e n t w i t h staphylococcal meningitis had moderate SNHL while one with meningococcal infection h a d m i l d h e a r i n g loss. A m o n g 26 patients with sterile CSF, 3 each had moderate and p r o f o u n d SNHL. But none of the organisms were significantly associated with a higher incidence of SNHL. The various other CSF correlates are s h o w n in Table 4. The only difference observed b e t w e e n the two g r o u p s w a s in the 2 ~d CSF s t u d y d o n e 48-72 h o u r s a f t e r a d m i s s i o n , in w h i c h the m e a n p e r c e n t a g e of p o l y m o r p h o n u c l e a r leukocytes and the protein content were significantly higher in those with SNHL. Aminoglycosides were used in 22 patients, 8 (36.4%) of w h o m d e v e l o p e d S N H L while one out of 10 patients (10%) in w h o m this was not used developed hearing loss. (p-0.12). Even w h e n the d u r a t i o n of a m i n o g l y c o s i d e t h e r a p y w a s t a k e n into c o n s i d e r a t i o n , there w a s no statistically significant difference between the various g r o u p s . (p=0.199) T h e r a p y c h a n g e s w e r e m a d e in 5 patients in w h o m the 2 nd CSF sample showed a rise in the cell counts. S N H L w a s o b s e r v e d in 3 (60%) of these patients as compared to 6 (22.2 %) out of 27 w h o did not have a change of antibiotics, the difference was again statistically not significant. (p value = 0.12). All significant variables which differed between the t w o g r o u p s , for e x a m p l e ; t o t a l d u r a t i o n of f e v e r , leucocytosis > 11000 per cumm, percentage of polymorphs Indian Journal of Pediatrics, Volume 69~November, 2002
Sensorineural Hearing Loss Following Acute Bacterial Meningitis TASTE 3. C l i n i c a l
Correlates
in SNHL
Group I (n = 23) Mean + SD
Group II (n = 9) Mean + SD
p value
35.87 + 35.72 3.13 + 2.43 0.56 + 1.12 0.739 + 0.75 1.478 + 3.54 0.56 + 0.78 5.30 + 13.69 1.04 + 0.97
19.00 + 28.57 5.33 + 4.5 0.111 + 0.33 1.22 + 1.64 9.33 + 16.73 1.333 + 2.179 11.88 + 20.46 1.55 + 1.74
0.72 0.19 0.31 0.63 0.30 0.26 0.16 0.61
2.56 + 1.77 8.521 + 4.56
3.88 + 3.95 13.00 + 6.42
0.59 0.04*
Group I (n = 23) Mean + SD
Group II (n=9) Mean + SD
p value
CSF I -Mean cell counts (cumm) - Neutrophils (%) - Protein (mg/dl) - Sugar (mg/dl)
1415.90 + 4090.78 55.4,5 + 25.49 92.86 + 84.30 57.36 + 23.41
4652.22 + 1308.6 62.66 + 25.30 149.33 + 122.13 43.33 + 27.44
0.61 0.39 0.13 0.13
CSF II - Mean cell counts (cumm) - Neutrophils (%) - Protein (mg/dl) - Sugar (mg/dl)
252.82 + 261.09 25.04 + 35.91 76.95 + 44.52 56.65 + 21.51
492.22 + 665.48 58.11 + 31.71 123.33 + 45.15 41.22 + 20.54
0.28 0.01" 0.009* 0.07
CSF IR - Mean ceil counts (cumin) - Neutrophils (%) - Protein (mg/dl) - Sugar (mg/dl)
38.41 + 114.11 12.0 + 26.38 51.0 + 21.72 62.8 + 40.31
100.85 + 159.54 30.0 + 29.86 126.66 + 135.36 55.33 + 16.99
0.08 0.07 0.31 0.58
Parameters
Age (months) Fever (days) Headache (days) Vomiting (days) Altered sensorium (hours) Seizures (days) Duration of seizures (minutes) Duration prior to antibiotic therapy (days) Interval between onset of symptoms and start of antibiotic therapy (days) Total duration of fever (days) * Significant (p < 0.05). T A e r E 4. C S F C o r r e l a t e s
in SNHL
Parameters
* Significant (p < 0.05) TABLI~ 5. P ~ d i c t e d
Proportion
CSF polymorphs II (%) 0 10 20 30 40 50 60 70 80 90 100
of
Hearing Impaired C h i l d r e n Predicted prob. SNHL 0.1265 0.1560 0.1909 0.2315 0.2777 0.3292 0.3851 0.~ 0.5052 0.5659 0.6246
polymorphs in the second CSF as the sole predictor variance. G i v e n a p e r c e n t a g e o f p o l y m o r p h s in t h e s e c o n d CSF analysis, probabilities of hearing impairment were derived using logistic regression program of BMDP software, University of California, Berkeley. The e s t i m a t e d c h a n c e s of h e a r i n g i m p a i r m e n t t h u s o b t a i n e d are g i v e n in Table 5. There is greater t h a n 50% p r o b a b i l i t y o f t h e p a t i e n t d e v e l o p i n g S N H L if t h e p e r c e n t a g e o f p o l y m o r p h s i n t h e s e c o n d C S F a n a l y s i s is 80% a n d it p r o g r e s s i v e l y rises if p o l y m o r p h s account for all the w h i t e cells. DISCUSSION
and protein levels in the second CSF analysis were s u b j e c t e d to s t e p w i s e l o g i s t i c r e g r e s s i o n a n a l y s i s . This p r o c e d u r e r e s u l t e d i n t h e s e l e c t i o n o f p e r c e n t a g e of polymorphs in the second CSF study as the single p r e d i c t o r of S N H L . T h e u s e of o t h e r v a r i a b l e s d i d n o t improve the prediction of SNHL. Hence logistic r e g r e s s i o n e q u a t i o n w a s d e r i v e d u s i n g the p e r c e n t a g e of
Indian Joumal of Pediatrics, Volume 69~November, 2002
The incidence of S N H L in the p r e s e n t s t u d y w a s 28.1% as s u g g e s t e d b y h e a r i n g t h r e s h o l d >30dB f o l l o w i n g ABM. Varying incidences have been reported worldwide from 9.7% to 36%. 6,7 T h e h e a r i n g loss w a s u n i l a t e r a l in 6.2% a n d bilateral in 21.9% in the p r e s e n t s t u d y . D a m o d a r a n et al r e p o r t e d a n incidence of unilateral h e a r i n g loss in 14.3%
953
B. Cherian et al and bilateral in 11.4%. 8 Taylor et al reported an incidence o f 11.3%, with 6.1% being unilateral and 5.2% bilateral. 9 Mild SNHL was observed in 3.1% and and moderate and p r o f o u n d SNHL in 12.5% each in the p r e s e n t s t u d y whereas in the one by Rasmussen et al using the same Davis and Silvermann hearing classification, mild was observed in 12.7%, severe in 1.1% and profound in 4.2%. l~ As observed in the present study (Table 2), several other authors too have noted that the age of the child did not correlate with the risk of SNHL? ,w13 The mean d u r a t i o n of fever at p r e s e n t a t i o n in the normal and hearing impaired groups was comparable, 3.1 and 5.3 days respectively (Table 3). Similar observations were made by Damodaran et al. 8 It is generally believed that a delay in diagnosis and t r e a t m e n t of bacteridl meningitis were important determinants of neurologic sequelae including deafness, but it is usually impossible to tell exactly when meningitis begins. TM When the total duration of fever was taken into account, the difference was f o u n d to be statistically significant. Kaplan et al examined specific time intervals and found that deafness was significantly higher in children who were ill for one day or less, 15whereas Salih et al had found duration of symptoms before treatment to correlate significantly with SNHL. 16 In the present study seizures did not correlate with the risk of developing SNHL as in other studies. 3-s,6 Seizures that present after the 4 th day, those that are difficult to treat and those that appear late in the course of meningitis are associated w i t h p o o r p r o g n o s i s and neurological sequelae. 17 T h e r e was o n l y one child w i t h n e u r o l o g i c a l complications in the hearing impaired group and this was a child with s u b d u r a l effusion w h o later d e v e l o p e d subdural empyema (Fig 1). Nadol et al had found higher incidence of SNHL in children w h o had neurological sequelae, ie coma, hemiplegia, cranial n e r v e palsies, h y d r o c e p h a l u s and s u b d u r a l e f f u s i o n , 11 w h i l e D a m o d a r a n et al did not find any correlation. 3 Prior antibiotic t h e r a p y s h o w e d no c o r r e l a t i o n w i t h d e v e l o p m e n t of SNHL in the present s t u d y which is similar to o t h e r s ) 8,~9 But Kaplan r e p o r t e d a h i g h e r incidence of SNHL and other neurlogical sequelae in p r e t r e a t e d children. 15 In the p r e s e n t s t u d y the CSF pleocytosis or neutrophil percentage at admission did not correlate significantly with SNHL although they were higher in the hearing impaired group. Similar reports were given by other investigators, s,2~ but Nadol in 1978 had proved the existence of positive correlation of CSF leucocytosis and subsequent SNHL in ABM. n Repeat CSF analysis and culture done after 48 hours of treatment showed a higher mean cell count in the hearing impaired g r o u p c o m p a r e d to the n o r m a l , b u t this was not significant. N e v e r t h e l e s s , the m e a n p e r c e n t a g e of polymorphs was found to have a strong correlation with SNHL, being higher in group II (58%) compared to 25% in group I. Similarly in the 3rd CSF s t u d y , the difference b e t w e e n the m e a n CSF c o u n t a n d p e r c e n t a g e of 954
p o l y m o r p h s displayed a trend t o w a r d s significance, hence proving the delayed clearing up of CSF to have a predictive value for d e v e l o p m e n t of SNHL following ABM. Literature review has not revealed any study in which follow up CSF has been analysed for pleocytosis. The CSF protein in the second sample too was found to be significantly higher in hearing impaired group compared to the normal. Damodaran et al in their pioneer study at New Delhi had also found higher CSF protein levels in the hearing impaired group but this was not statistically significant. There were no details about the subsequent CSF protein analysis. 3 Although the mean CSF sugar was lower in group II, the difference was not significant. The present study did not find any particular organism to be associated with a higher incidence of SNHL even t h o u g h 3 o u t of 9 cases w i t h S N H L w e r e d u e to meningococcus. In a study at Saudi Arabia it was found that even though the incidence of H.influenzae meningitis was m o r e , the e x t e n t of d a m a g e to the n e r v e was maximum following meningococcal meningitis, z2Various o t h e r a u t h o r s h a v e r e p o r t e d p n e u m o c o c c u s to be notorious for causing grave neuroaudiological damageY 3" 23
Aminoglycosides are known to cause ototoxicity in humans. In the present study there was no significant difference in the incidence of ototoxicity between those who received aminoglycosides and those who did not. This may be because the younger patients are less likely to develop ototoxicity compared to the older ones. The degree of dysfunction depends on the number of sensory hair cells and there a p p e a r s to be a decrease in the number of cells with age. 24 Probabilities of SNHL was estimated based on the clinical data of p measurements of interest made on the child. The application of multiple logistic model provides these estimates of risk. Positive values of I are signs of poor prognosis while negative score correspond to lower risk patients. There is a greater than 50% probability of the p a t i e n t d e v e l o p i n g S N H L if the p e r c e n t a g e of polymorphs in the second CSF analysis is 80% and it rises to 62% if the polymorphs account for all the white cells. CONCLUSION Sensonneural hearing loss was noted in 28.1% of the nonneonates admitted with ABM. Age and sex of the patient or aminoglycoside usage did not have any association w i t h SNHL. Patients w i t h l o n g e r d u r a t i o n of f e v e r throughout the course of the illness had higher incidence of SNHL. A higher percentage of polymorphs and raised p r o t e i n content in the second CSF analysis s h o w e d significant c o r r e l a t i o n w i t h risk of S N H L a n d the probability of developing SNHL is greater than 50% if polymorphs account for 80% or more of the cells in the second CSF. It is worthwhile p e r f o r m i n g BERA in all patients with ABM since there is a significant risk of developing SNHL, more so if the second CSF analysis Indian Journal of Pediatrics, Volume 69--November, 2002
Sensorineural Hearing Loss Following Acute Bacterial Meningitis shows p o l y m o r p h o n u c l e a r pleocytosis as this m a y help i n p r o v i d i n g early i n t e r v e n t i o n to these children. REFERENCES
1. Mason AJ, Herrmann RK. Universal infant hearing screening by automated auditory brainstem response measurement. Pediatrics 1998; 101 : 221-228. 2. Fortnum HM. Hearing impairment after bacterial meningitis: a review. Arch Dis Child 1992; 1128-1133. 3. Damodaran A, Aneja S, Malhotra VL. Sensorineural hearing loss following acute bacterial meningitis. A prospective evaluation. Ind Pediatr 1996; 33 : 763-766. 4. Aneja S, Aggarwal A. Acute bacterial meningitis. Ind Pediatr 1997; 34 : 1097-1109. 5. Dodge RP, Davis H, Feigin DR et al. Prospective evaluation of hearing impairment as a sequela of acute bacterial meningitis. NEnglJMed 1984; 311 (14) : 869-874. 6. Pomeroy LS, Sandra JH, Dodge PR. Seizures and other neurologic sequelae of bacterial meningitisin children. N Engl JMed 1990;323 : 1651-657. 7. Lebel MH, Hoyt J, Waagner DC, Rollins NK, Finitzo T, McCracken GH. Magnetic Resonance Imaging and Dexamethasone Therapy for Bacterial Meningitis. Am J Dis Child 1989; 143 : 301-306. 8. Damodaran A, Aneja S, Malhotra VL: Sensorineural hearing loss following acute bacterial meningitis. A prospective evaluation. Ind Pediatr 1996;33 : 763-766. 9. Taylor GH, Milkis LE, Clampi A, Berger DU, Watters VG, Gold R et al. The sequelae of haemophihis influenzae meningitis in school age children. N Engl JMed 1990; 323 : 1657-63. 10. Rasmussen N, Johnsen JN, Bohr AV. Otologic sequelae after pneumococcal meningitis: A survey of 154 consecutive cases with a follow up of 94 survivors. Laryngoscope 1991; 101 : 876882. 11. Nadol JB: Hearing loss as a sequela of meningitis. Laryngoscope 1978; 88 : 739-755.
Indian Joumal of Pediatrics, Volume 69--November, 2002
12. Dodge RP, Davis H, Feigin DR et al. Prospective evaluation of hearing impairment as a sequela of acute bacterial meningitis. N EnglJ Med 1984;311 (14) : 869-874. 13. Ozdamar O, Kraus N, Stein L. Auditory brainstem responses in infants recovering from bacterial meningitis. Arch Otolaryngo11983; 109 : 13-18. 14. Kilpi T, Anttila M, Markku J, KaUio T, Peltola H. Severity of childhood bacterial meningitis and duration of illness before diagnosis. Lancet 1991; 338 : 406-409. 15. Kaplan LS, Smith OE, Wills C, Feigin DR. Association between preadmission oral antibiotic therapy and cerebrospinal fluid findings and sequelae caused by haemophilus influenzae type b memigitis. Pediatr Infect Dis 1986; 5 (6) : 626-632. 16. Salih MAM, Khaleefa HO, Bushara M: Long term sequelae of childhood. Acute bacterial meningitisin a developing country. Scand J Infect Dis 1991; 23 : 175-182. 17. Jayakumar V. Current therapy of Pyogenic Meningitis. IAP J Pract Pediatr 2000; 2: 43-50. 18. Herson CV, Todd KJ. Prediction of morbidity in hemophilus influenzae meningitis. Pediatrics 1977;59 (1) : 35-39. 19. Feldman MH, Michaels HR. Academic achievement in children ten to 12 years after haemophilus influenzae meningitis. Pediatrics 1988; 81 : 339-344. 20. Vienny H, Despland PA, Liitschg J. Early diagnosis a n d evolution of deafness in childhood bacterial meningitis: A study using brainstem auditory evoked potentials. Pediatrics 1984; 73 : 579-586. 21. Kotagal S, Rosenberg C, Rudd D, Dunlde ML, Horenstein S. Auditory evoked potentials in bacter~l meningitis. Arch Neurol 1981; 38 : 693-695. 22. Ashraf H. Changes in auditory brainstem response as a sequele of bacterial meningitis. Ind J Oto11999; 5 (1) : 45-48. 23. BaraffJH, Lee IS, Schriger DL. Outcome of bacterial meningitis in children: a meta analysis. Pediatr Infect Dis J 1993; 12 : 389-94. 24. Sande MA, MandeU GL. Antimicrobialagents. In Gilman AG, Rall TW, Nies AS, Taylor P, eds. The Pharmacological Basis of Therapeutics. 8~ edn. New York, Pergamon Press, 1990: pp 1098-1116.
955