Schonfeld H, Helwig H (eds): Bacterial Meningitis. Antibiot Chemother. Basel, Karger, 1992, vol 45, pp 209-217

Sequelae of Acute Bacterial Meningitis in Children Amin Kabani, Taj Jadavji Alberta Children's Hospital, University of Calgary, Alta., Canada

Acute Bacterial Meningitis

Prognosis and Sequelae The prognosis in individual patients with bacterial meningitis is dependent on many variables including age at onset of disease, duration of illness prior to onset of effective therapy, the specific microorganisms

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Bacterial meningitis still remains a very significant problem in the antibiotic era, with an estimated 15,000 children being affected in the United States each year [1, 2] . The peak incidence occurs between 6 and 9 months of age and falls rapidly after the age of 3 years. Haemophilus inJiuenzae type b meningitis accounts for 30-70 cases/100,000 followed by Neisseriae meningitidis and Streptococcus pneumoniae. Despite rapid institution of appropriate antibiotics and supportive care, children still die from this disease. However, some major gains have been made over the last half a century as far as mortality is concerned. Prior to 1940, H. inJiuenzae type b was associated with a mortality of 90-100% [3]. With the introduction of antibiotics the mortality has decreased to between 5 and 10% [4]. With this decrease in mortality it became evident that more children were surviving with long-term neurologic sequelae. Sproles et aI. [5] and Sell et at. [6], in retrospective studies, showed that the outcome of bacterial meningitis was poor, with a morbidity of 43% and only 43-45% of the children having a normal outcome. These studies were limited by their retrospective design and an inability to control for numerous variables. Since then a number of prospective studies have been done to evaluate the long-term sequelae of meningitis, and these give reason for cautious optimism [7-10] .



Table 1. Neurologic complications of bacterial meningitis Toxic encephalopathy Cerebral edema Acute - - - - - - I Brain herniation Cranial nerve palsies/deafness SIADHlD1 Seizures Subdural effusions Mycotic aneurysms Subacute Cortical vein thrombosis/cerebral infarction Motor deficits Hydrocephalus Arachnoiditis Spinal root/nerve palsies Deafness Chronic----i Mental retardation Speech abnormalities Seizures Behavior disorders/learning disorders/attention deficits Decreased intelligence quotients

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) SIADH in children with bacterial meningitis has been documented in many studies. Feigin et al. [13] noted an incidence of 88% in children with meningitis and showed that the levels of ADH were greater in these children compared to febrile or normal children. The precise mechanism is unknown but enhanced release of vasopressin from the supraopticohypophyseal system secondary to inflammation has been postulated [14]. The importance of this observation is the finding that prolonged depres-

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causing disease, the number of microorganisms or quantity of active bacterial products in the cerebrospinal fluid (CSF) [11], and the host inflammatory response [12]. The complications of bacterial meningitis may be divided into acute, subacute and late complications (table 1). The focus of this article will be primarily on the late sequelae of bacterial meningitis defined as abnormalities that persist for 3 years or more, and are permanent. The early identification of these long-term complications, and factors predisposing to them, may enable appropriate early intervention and remediation in order to minimize the secondary consequences of these disabilities. Prior to discussing these long-term neurologic complications there are a few acute and subacute complications which bear special attention.

Sequelae of Acute Bacterial Meningitis in Children


sion of serum sodium has been correlated with the presence of neurologic abnormality at 1 month following discharge [13]. Subdural Effusion (SDE) McKay et al. [15] were the first to notice that SDE were quite common, occurring in 33% of their patients. Following that report it became common practice to treat the effusions with repeated needle aspirations or surgical drainage. It also became evident that the harder one looked for SDE, the more one found them. Platou et al. [16] in a retrospective study found a higher incidence of neurologic sequelae in patients with SDE. Since then, other studies [16, 17] have confirmed the frequent occurrence of SDE (39%) but concluded that the effusions are not the cause of neurologic sequelae. These neurologic complications are better ascribed to other concomitant pathogenic mechanisms such as higher CSF bacterial load, vasculitis or infarction, and although patients with SDE are more likely to have acute complications such as seizures, persistent fever and focal neurologic deficits, there is no correlation with long-term sequelae. Furthermore, there was no case of SDE that lasted more than 3 months, and specific invasive therapy was not required if the patients were otherwise improving. Seizures (Acute) Seizures during the acute stage of meningitis are very common [2, 8, 18]. They occur in 17% of patients prior to admission and up to 26% of patients within 48 h of admission. Overall, seizures are noted in 30% of patients with bacterial meningitis. In one recent retrospective study, 67% of seizures were partial, generalized with focal predominance or partial with secondary generalization [8]. Generalized seizures or those occurring in the first 72 h of hospitalization generally do not predict long-term sequelae. Late or focal seizures may be due to SDE, abscess formation, thrombosis, cerebral infarction or SIADH and therefore appropriate studies may be required to rule out correctable causes of seizures. Despite the high frequency of acute seizures, only 7% will have late afebrile seizures [8].

Since the publication of earlier studies [5, 6] there have been a number of good retrospective and prospective studies which have helped to define the long-term complications of bacterial meningitis (table 2). These studies have also delivered some helpful prognostic factors [7-11,13,19].

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Long- Term Sequelae



Table 2. Sequelae of bacterial meningitis reported in literature Author

Sproles [5]

Sell [6]

Sell [24]

Feigin [13]

Sell [23]


1951-64 retrospec.

1950-64 retrospec.

1960-64 retrospec.

1974-76 prospec.

1975-76 prospec.

Age group, months







H. inftu.

H. inftu.

H. inftu.

H. inftu.

H. inftu.

H. men.

S. pneu. Follow-up period years


school age

school age








Other, %



Mortality, %



Normal, %



6 sign if.




13 50

Hearing Deficit Probably the most precisely quantitated sequelae of bacterial meningitis is hearing loss, which is also the most frequent complication of meningitis. Dodge et al. [19] in their prospective study found an overall incidence of bilateral or unilateral sensorineural hearing loss (SNHL), as determined by electric response audiometry and conventional tests, to be 10.3%. Patients with S. pneumoniae had the highest incidence of 31%, followed by N. meningitidis at 10.5% and H. inJluenzae at 6%. Similar results were obtained by Jadavji et al. [9] with an overall incidence of SNHL of 12.9%; 43.3% for S. pneumoniae and 7.3% for H. inJluenzae. Two other recent studies [7, 8] also show an overall incidence of SNHL of 11-20%. Most interesting is the study by Lebel et al. [lOJ who in a double-blind, placebo-controlled study evaluated the efficacy of dexamethasone, given early in bacterial meningitis. They showed a decrease in the moderate to severe hearing loss in the dexamethasone group versus the placebo group (3.3 vs. 15.5%), and a 1 vs. 14% difference between the two groups, for severe to profound hearing loss. Studies from Costa Rica [20], recently presented, substantiate these early results. Some studies have noted a very high incidence of hearing loss, these varying figures may relate to the severity of the disease on admission, the

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Sequelae SNHL,%



Sequelae of Acute Bacterial Meningitis in Children

Feldman [11]

Dodge [19]

Jadavji [9]

Lebel [10]

Pomeroy [8]

Taylor [7]

"'1980 prospec.

1973-77 prospec.

1979-83 prospec.

1984-85 prospec.

1973-77 prospec.

1972-84 prospec.






m= 17

H. influ.

H.influ. N. men. S. pneu.

H. influ. N. men.

H. influ. N. men. S. pneu. other

H. influ. N. men.

H. influ.
















14 placebo/ 1 steroid





S. pneu.

7 6.4 80


0.5 86

Seizures As noted above, seizures are a frequent complication in the early stages of meningitis. However, seizures occurring as late sequelae of meningitis have been reported in only 2-8% [7-9, 23]. A recently published study by Pomeroy et al. [8] showed that although 31 % of patients had seizures in the acute phase, only 7% had one or more late afebrile seizures, and the children with persistent neurologic deficits were most at risk. They also showed that children with a normal neurologic exam at 6 weeks following meningitis were likely to escape the sequelae of 'epilepsy'. Seizures occurring during acute meningitis were highly associated with subsequent late seizures and persistent neurologic deficits ; however, the vast majority of children with acute' seizures had a normal outcome. Most of the seizures occurred within 5 years of the meningitis.

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etiologic agents, and the methodology used to evaluate hearing loss [21]. Age of onset of meningitis and the duration of illness prior to the onset of treatment has no adverse effect on hearing loss [19]. The deafness is generally noted early in the course of bacterial meningitis [10, 21-23] and occasionally the hearing loss may improve with time [7].



Language Disorder The frequency of language disorder or delay has been commented on by a number of investigators. Jadavji et al. [9] detected only a 5% incidence in their 1-year follow-up study, while Feldman et al. [11] noted an incidence of 34%; 27% had delayed speech while 7% had expressive language deficits. Sell [23] noted a 15% incidence of receptive or expressive language developmental delay. Taylor et al. [7] in a sibling-controlled follow-up of children with meningitis found that these children had poorer reading skills and were more likely to be getting specialized educational assistance.

Motor Abnormalities Motor abnormalities have been reported in 3-7% of survivors of bacterial meningitis [9, 23]. Feigin et al. [13] showed that although paresis was not uncommon during acute infection (16%), marked improvement occurred weeks to months later, with persistent abnormality in only 4% of cases. Further, Pomeroy et al. [8] had 37% of patients who had acute neurologic deficits. In more than 60% of these patients the abnormalities

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Mental Retardation The frequency of intelligence quotient scores (IQ) of less than 70 has been reported at approximately 10% [23]. Sell et al. [24] in a follow-up study of 21 postmeningitis children, in comparison to their siblings, showed a mean IQ significantly lower in the index group, 29% of survivors scored less than 1 SD (15 IQ points) below their controls. They also showed that in comparison to age- and sex-matched peers in the same class, the postmeningitic group had statistically inferior performances to their peers. Feigin et al. [13] had 6% of patients who had an IQ of less than 70 and 28% with IQ between 70 and 90, while Jadavji et al. [9] had only 5% of their patients with demonstrable developmental delay, however, no control group was used in that study. Taylor et al. [25] showed that children who had meningitis performed poorly compared to their age-matched siblings on performance IQ and full-scale IQ but not verbal IQ, and they compared favorably on all academic measures. Recently the Canadian group has reported the largest series of siblingcontrolled developmental outcomes, and their results are very optimistic. Of 58% of children without any acute phase neurologic sequelae, there was no difference between the index group and their siblings in all measures. Of 41 pairs in which the index child had an acute neurological complication, the full-scale IQ score was 102 vs. 109 for the sibling [7]. These studies show that the neurologic outcome may be subtle and better than initially predicted.

Sequelae of Acute Bacterial Meningitis in Children


resolved within 3 months, and in 2 patients within 12 months. These abnormalities included 11% hemiparesis, 4% ataxia, 3% cranial nerve deficits (excluding sensorineural hearing loss), 6% with extensor plantar responses, and 2% with brisk reflexes. There were only 8 patients (4%) with residual hemiparesis or quadriplegia. These studies indicate that even gross acute motor abnormalities have a potential to resolve, however there are very few clues to predict outcome in individual patients [8, 11]. Why these abnormalities occur and resolve is not known, and is variously ascribed to the 'plasticity' of the brain. It is more likely that reversible trauma may cause reversible findings as opposed to significant trauma. This theory is substantiated by cr scans always being abnormal in patients with permanent sequelae while in all but 2 of the patients with transient neurologic abnormality the CT scans were normal [8]. Visual Impairment Visual impairment has been found in 2-4% of survivors [9, 23, 26]. In cases where extensive radiologic and electrophysiologic studies have been done, reversible abnormality of vision is due to vasospasm of the arteries while permanent visual impairment is due to cerebral occipital hemorrhage and atrophy. Other Complications Other complications of meningitis have included hydrocephalus 1.7% and isolated cranial nerve palsies besides sensorineural hearing loss [9]. Ataxia occurred in 4% of cases and may be a presenting symptom, however it persisted in only 0.5% of cases. It is also associated with SNHL, implying a combined insult to the vestibulocochlear system [13, 27]. More subtle findings of attention deficits and behavioral problems have been reported [7, 24] and are thought to be more pervasive than documented. Older children, primarily boys, and those from lower socioeconomic classes are particularly at risk. The socioeconomic. status certainly places the high-risk patients at an even higher risk compared to their more privileged peers.

In the last 50 years the mortality of bacterial meningitis has been reduced to between 5 and 10% [9] and in many centers to less than 5% [13]. The morbidity still remains high, however there are some recently published studies that indicate that the long-term prognosis may not be as gloomy as initially thought to be [7, 8, 10]. Recent studies, involving the

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Future Outlook



modulation of host immune and inflammatory response, in clinical and experimental meningitis suggest that there may be a beneficial effect In decreasing the long-term neurologic sequelae when agents such as steroids are used [10, 12, 28, 29]. However, these studies need to be replicated in other centers, over a wide range of populations, prior to their use becoming a standard recommendation. References Stutman HR, Marks MI: Bacterial meningitis in children: diagnosis and therapy. A review of recent developments. Clin Pediatr (Phila) 1987;26:431-438. 2 Klein JO, Feigin RD, McCracken GH Jr: Report of task force on diagnosis and management of meningitis. Pediatrics 1986;78:959-982. 3 Crook WG, Clanton BR, Hodes HL: Haemophilus inJluenzae meningitis: Observation on the treatment of 110 cases. Pediatrics 1949;4:643 4 Nyhan WL, Richardson F: Complications of meningitis. Annu Rev Med 1963;14:243. 5 Sproles ET III, Azerrod J , Williamson C, Merrill RE: Meningitis due to Haemophilus inJluenzae: long-term sequelae. J Pediatr 1969;75:782-788. 6 Sell SHW, Merrill RE, Doyne EO, Zimsky ED Jr: Long-term sequelae of HaemophiIus inJluenzae meningitis. Pediatrics 1972;49:206-21l. 7 Taylor GH, Mills EL, Gampi A, Du Berger R, Watters GV, Gold R, MacDonald N, Michaels R: The sequelae of Haemophilus inJluenzae meningitis in school age children. N Engl J Med 1990;323:1657-1663. 8 Pomeroy SL, Holmes SJ, Dodge PR, Feigin RD: Seizures and other neurologic sequelae of bacterial meningitis in children. N Engl J Med 1990;323:1651-1657. 9 Jadavji T, Biggar W, Gold R , Prober C: Sequelae of bacterial meningitis in children treated for seven days. Pediatrics 1986;78:21-25. 10 Lebel MH, Freij BJ, Syrogiannopoulos GA, Chrane DF, Hoyt MS, Stewart SM, Kennard BD , Oslen KD , McCracken GH: Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo controlled trials. N Engl J Med 1988; 319:964-971. 11 Feldman WE, Ginsburg CB, McCracken GH, Allen D, Ahmann P, Graham J , Graham L: Relation of concentrations of Haemophilus inJluenzae type b in cerebrospinal fluid to late sequelae of patients with meningitis. J Pediatr 1982;100:209-218. 12 Mustafa MM, Lebel MH, Ramilo 0, Olsen KD, Reisch JS, Beutler B, McCracken GH Jr: Correlation of interleukin-lf3 and cachectin concentrations in cerebrospinal fluid and outcome of bacterial meningitis. J Pediatr 1989;115:208-213. 13 Feigin RD, Stechenberg BW, Chang MJ, Dunkle LM, Wong ML, Pakes H, Dodge PR, Davis H: Prospective evaluation of treatment of Haemophilus inJluenzae meningitis. J Pediatr 1976;88:542-548. 14 Reynolds DW, Dweck HS, Cassady G: Inappropriate antidiuretic hormone secretion in a neonate with meningitis. Am J Dis Child 1972;123:251-253. 15 McKay JR, Marrisette RA, Ingraham FD, Matson DD: Collections of subdural fluid complicating meningitis due to Haemophilus inJluenzae (type b) . A preliminary report. N Engl J Med 1950;242:20-21. 16 Platou R, Rinker A , Derrick J: Acute subdural effusions and late sequelae of meningitis. Pediatrics 1959;23:962-971.

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Sequelae of Acute Bacterial Meningitis in Children

18 19 20 21 22 23 24 25 26 27 28 29

Snedeker JD, Kaplan SL, Dodge PR, Holmes SJ, Feigin RD: Subdural effusion and its relationship with neurologic sequelae of bacterial meningits in infancy: A prospective study. Pediatrics 1990;36:163-170. Feigin RD, Dodge PR: Bacterial meningitis: Newer concepts of pathophysiology and neurologic sequelae. Pediatr Clin North Am 1976;23:541-556. Dodge PR, Davis H, Feigin RD, Holmes SJ, Kaplan SL, Jubeliner D, Stechenberg BW, Hirsch SK: Prospective evaluation of hearing impairment as a sequelae of bacterial meningitis. N Engl J Med 1984;311:869-874. Odio M, Faingezicht I, Paris M, Saez-Llorens X, McCracken GH Jr: Double-blinded, randomized, placebo-controlled trial of dexamethasone therapy for bacterial meningitis Pediatr Res 1990;27:178(abstr 1054). Vienny H, Despland PA, Lutschg J, Deonna T, Dutoit-Marco ML, Gander C: Early diagnosis and evaluation of deafness in childhood bacterial meningitis: a study using brainstem auditory evoked potentials. Pediatrics 1984;73:579-586. Kaplan SL, Catlin Fl, Weaver T, Feigin RD: Onset of hearing loss in children with bacterial meningitis. Pediatrics 1984;73:575-578. Sell SW: Long-term sequelae of bacterial meningitis in children. Pediatr Infect Dis J 1983;2:90-93. Sell SHW, Webb WW, Pate JE, Doyne EO: Psychological sequelae of bacterial meningitis: Two controlled studies. Pediatrics 1972;49:212-217. Taylor GH, Michaels RH, Mazur PM, Bauer RE, Liden CB: Intellectual, neuropsychological and achievement outcomes in children six to eight years after recovery from Haemophilus injluenzae meningitis. Pediatrics 1984;74:198-205. Teppenberg J, Nussbaum E, Feldman F: Cortical blindness following meningitis due to Haemophilus injluenzae type b. J Pediatr 1977;91:434-436. Kaplan SL, Goddard J, Van Kleeck M, Catlin FJ, Feigin RD: Ataxia and deafness in children due to bacterial meningitis. Pediatrics 1981;68:8-13. Sande MA, Scheid WM, McCracken GH Jr, and the Meningitis Study Group: Report of a workshop: Pathophysiology of bacterial meningitis - implications for new management strategies. Pediatr Infect Dis J 1987;6:1145-1171. Mustafa MM, Ramilo 0, Saez-Llorens X, Olsen KD, Magness RR, McCracken GH Jr: Cerebrospinal fluid prostaglandins, interleukin-l/3, and tumour necrosis factor in bacterial meningitis: clinical and laboratory correlations in placebo and dexamethasone treated patients. Am J Dis Child 1990;144:883-887.

Dr. Taj Jadavji, Alberta Children's Hospital, 1820 Richmond Rd. SW, Calgary, Alta. T2T SC7 (Canada)

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Sequelae of acute bacterial meningitis in children.

Schonfeld H, Helwig H (eds): Bacterial Meningitis. Antibiot Chemother. Basel, Karger, 1992, vol 45, pp 209-217 Sequelae of Acute Bacterial Meningitis...
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