Table 3 Study characteristics of studies on prediction of sequelae after bacterial meningitis.

Forsyth et al., 2004 [18]

Prospective

Developing (Malawi)

343

2 months - 13 yr

All

1 and 6 months after discharge

Hearing loss

Univariate

Coma, positive CSF Gram stain, a low peripheral WBC count, high CSF protein level, associated neurological sequelae

Koomen et al., 2003 [7]

Retrospective

Developed (The Netherlands)

628

0 - 9.5 yr (mean 2.4yr)

Non Hib

Hearing loss

Multivariate

History of symptoms >2 days, absence petechiae, low CSF glucose level, causative pathogen (S. pneumoniae), ataxia

Woolley et al., 1999 [9]

Retrospective

Developed (UK)

432

Median 7.7 months

All

6 months intervals for at least 1 yr (range 1-5 yr)

Hearing loss

Multivariate

Male sex, increased ICP, low CSF glucose level, causative pathogen (S. pneumoniae), presence nuchal rigidity

Kutz et al., 2006 [14]

Retrospective

Developed (USA)

171

3 months 17 yr (mean 3.8 yr)

All

During hospitalization (longer if necessary)

Hearing loss

Univariate

Long duration hospitalization, cranial nerve neuropathy, low CSF glucose level, high CSF protein level,

seizures (not significant in case of S. pneumoniae)

Lovera et al., 2005 [33]

Retrospective

Developing (Paraguay)

72

35 days - 15 yr (mean 48 months)

S. pneumoniae

During hospitalization

Mortality

Univariate

Age <12 months, coma, seizures, prolonged duration of seizures >48 h, low CSF WBC count, high CSF protein (albumin) level, low CSF glucose level, low peripheral WBC count, low Hb

Roine et al., 2008 [35]

Prospective

Developing (6 countries in Latin America)

654 total cohort, 332 included in analysis

Median 8 months in patients who died, median 12 months in survivors (not otherwise reported)

all

During hospitalization

Mortality

Multivariate

Impaired consciousness, poor peripheral circulation, high CSF protein level

Pelkonen et al., 2009 [6]

Retrospective

Developing (Angola)

403 total cohort, 290 included in analysis

Median 9.0 months

All

During hospitalization

Mortality

Multivariate

Impaired consciousness, severe dyspnea, convulsions during hospitalization

Kornelisse et al., 1995 [8]

Retrospective

Developed (The Netherlands)

83

3 days- 12.3 yr (median 8 months)

S. pneumoniae

During hospitalization

Mortality

Univariate

Comatose level of consciousness, shock, respiratory distress, low peripheral WBC count, low serum sodium level, high CSF protein level

Fakhir et al., 1992 [27]

Retrospective

Developing (India)

247

1 month - 14 yr

N. meningitidis

During hospitalization

Mortality

Univariate

Illness duration <12 h, hypotension, peripheral circulatory failure, coma (disturbed sensorium), rash duration <12 h, rash extent widespread, fever >40°C, absent neck rigidity, low peripheral WBC count, low ESR, low platelet count

Akpede et al., 1999 [16]

Prospective

Developing (Nigeria)

109

>1 month - 15 yr

All

During hospitalization (after discharge?)

Mortality

Univariate

Seizures, coma, shock

Wasier et al., 2005 [37]

Retrospective

Developed (France)

49

1 - 108 months (median 17 months)

S. pneumoniae

1-12 yr (mean 5 yr)

Mortality

Multivariate

High PRISM II score, low peripheral WBC count, low platelet count

Chao et al., 2008 [26]

Retrospective

Developing (Taiwan)

37

3 months - 11 yr (mean 37 months)

S. pneumoniae

Mortality

Univariate

Coma, shock, mechanical ventilation (endotracheal tube intubation), hyponatremia, low CSF WBC count, low CSF glucose level, low CSF/blood glucose ratio

Johnson et al., 2007 [28]

Retrospective

Developing (Nigeria)

71

<16 yr

All

During hospitalization

Mortality

Univariate

Respiratory distress, purulent/turbid CSF appearance, high CSF protein level, low CSF glucose level

Bortolussi et al., 1978 [25]

Retrospective

Developed (Canada)

52

Neonates (<1 month)

All

During hospitalization

Mortality

Univariate

low peripheral WBC count, thrombocytopenia, low birth weight <2500 g

Study

Design

Developed or developing (Country)

N

Age at infection

Pathogen

Follow-up duration

Outcome: sequelae

Analysis

Significant prognostic factors

From multivariate analysis

Or from univariate analysis with p < 0.05

Koomen et al., 2004 [5]

Retrospective

Developed (The Netherlands)

182

0 - 9.5 yr

(mean 2.4yr)

Non- Hib

4.0 - 10.4 yr post meningitis (average 7.4 yr)

Neurological sequelae

Academic & behavioural limitations

Multivariate

male gender, low birth weight ≤3000 g, low educational level father, causative pathogen (S. pneumoniae), low CSF WBC count, delay >6 h start antibiotics, dexamethasone use ≤2 days, anticonvulsive treatment of seizures, prolonged fever >9 days

Pelkonen et al., 2009 [6]

Retrospective

Developing (Angola)

403 total cohort, 249 survivors, 200 included in analysys

Median 9.0 months

All

During hospitalization

Severe neurological sequelae

Multivariate

History of symptoms >3 days, impaired consciousness, convulsions during hospitalization

Biesheuvel et al., 2006 [24]

Retrospective

Developed (The Netherlands)

88 (derivation)

628 (validation)

0.9 - 5.8 yr (mean 2.8 yr) (derivation) and 0 - 9.5 yr (mean 1.9 yr) (validation)

Non Hib

Neurological sequelae

Both mild and severe

Multivariate

Seizures (atypical convulsions), absence petechiae/ecchymoses, low body temperature <40°C, high body temperature/fever >40°, causative pathogen (S. pneumoniae), use of anti epileptic drugs >2 days

Singhi et al., 2007 [15]

Prospective

Developing (India)

80

2 months - 12 yr (mean 31.4 months)

All

12-44 months after discharge (mean 27.5 months)

Neurological sequelae

Both mild and severe

Multivariate

coma, cranial nerve palsy, absent deep tendon reflexes

Kornelisse et al., 1995 [8]

Retrospective

Developed (The Netherlands)

83

3 days- 12.3 yr (median 8 months)

S. pneumoniae

Hospital duration

Neurological sequelae

Both mild and severe

Univariate

High clinical severity score (Herson & Todd score), vomiting, shock, low peripheral WBC count, low CSF WBC count, low CSF glucose level

Akpede et al., 1999 [16]

Prospective

Developing (Nigeria)

109

>1 month - 15 yr

All

During hospitalization (after discharge?)

Neurological sequelae

Both mild and severe motor and sensory sequelae

Univariate

Young age ≤2 yr, seizures, coma, prolonged fever >7 days, antibiotic treatment, focal nerve deficits, abnormal posturing, abnormal muscle tone

Pikis et al., 1996 [20]

Retrospective

Developed (Greece)

47

1 month - 14 yr (mean 2.6 yr)

S. pneumoniae

4- 23 yr (mean 12.4 yr)

Neurologic sequelae

Both mild and severe

Multivariate

Coma, high peripheral WBC count

Pomeroy et al., 1990 [34]

Prospective

Developed (USA)

185

1 month - 14 yr (median 10 months)

All

1,3,6,12, months after discharge and yearly up to 6 yr

Neurologic sequelae

Both mild and severe

Univariate

Seizures, low CSF glucose level

Chao et al., 2008 [26]

Retrospective

Developing (Taiwan)

37

3 months - 11 yr (mean 37 months)

S. pneumoniae

Neurological sequelae

Both mild and severe lasting >6 months

Univariate

Focal neurological signs, seizures

Study

Design

Developed or developing (Country)

N

Age at infection

Pathogen

Follow-up duration

Outcome: poor outcome

Analysis

Significant prognostic factors

From multivariate analysis

Or from univariate analysis with p < 0.05

Lovera et al., 2005 [33]

Retrospective

Developing (Paraguay)

72

35 days - 15 yr (mean 48 months)

S. pneumoniae

During hospitalization

Mortality & neurological sequelae

Univariate

Young age <12 months, coma, seizures, seizure duration >48 h, low CSF WBC count, high CSF protein (albumin) level, low CSF glucose level, low peripheral WBC count, low Hemoglobin

Oostenbrink et al., 2002 [21]

Retrospective

Developed (The Netherlands)

93

1 month - 15 yr (median 2.8 yr)

Non Hib

0.6 yr

Mortality & neurological sequelae

Multivariate

male gender, seizures (atypical convulsions), low body temperature, causative pathogen (S. pneumoniae)

Roine et al., 2008 [35]

Prospective

Developing (6 countries in Latin America)

642 total cohort, 356 included in analysis

Median 7 months in patients whith positive outcome measure died, median 14 months in patients without (not otherwise reported)

all

During hospitalization

Mortality & severe neurological sequelae

Multivariate

Impaired consciousness, history of symptoms >48 h, high CSF protein level, low peripheral WBC count

Roine et al., 2008 [35]

Prospective

Developing (6 countries in Latin America)

641 total cohort, 296 included in analysis

Median 7 months in patients whith positive outcome measure died, median 18 months in patients without (not otherwise reported)

all

During hospitalization

Mortality & all neurological sequelae

Multivariate

Impaired consciousness, convulsions before admission, poor peripheral circulation, low CSF glucose level, low peripheral WBC count

Pagliano et al., 2007 [19]

Prospective

Developed (Italy)

64

1 month -14 yr (median 26 months)

S. pneumoniae

8 weeks

Mortality & neurological sequelae

Multivariate

ICU admission, low CSF WBC count, penicillin nonsusceptibility

Klinger et al., 2000 [31]

Retrospective

Developed (Canada)

101

Neonates 1-28 days

All

1 yr

Mortality & neurological sequelae

Univariate

Hypotension, coma, inotrope, seizure duration >12 h, status epilepticus, low CSF/blood glucose level, low peripheral WBC count, abnormal neurological examination at discharge, ventilation, no. of anticonvulsants

Klinger et al., 2000 [31]

Retrospective

Developed (Canada)

101

Neonates 1-28 days

All

1 yr

During hospitalization,

Mortality & neurological sequelae

*multivariate analysis

* For different time schedules during and after hospital admission not presented here

Akpede et al., 1999 [16]

Prospective

Developing (Nigeria)

109

>1 month - 15 yr

All

Possibly after discharge in neurologic clinic

Mortality & neurological sequelae

Univariate

Young age ≤2 yr, seizures, coma, shock, prolonged fever, >7 days antibiotic treatment, no meningeal signs, focal nerve deficits, abnormal posturing, abnormal muscle tone

Kaaresen et al., 1995 [29]

Retrospective

Developed (Norway)

92

Median 1.9 yr

(range 1 month - 13.8 yr)

All

Hospital duration and mean 6 weeks afterwards, or longer if necessary

Mortality & neurological sequelae

Multivariate

History of symptoms >48 h, seizures, high body temperature,>38 °C, peripheral vasoconstriction, low CSF WBC count

Grimwood et al., 1996 [12]

Prospective

Developed (Australia)

138

3 months - 14 yr

All

Mean 6.7 yr post meningitis (range 5.3-9.3 yr)

Mortality & neurological sequelae

Multivariate

Young age ≤12 months, long symptom duration before diagnosis >24 h, seizures >72 h, focal neurological signs

Edwards et al., 1985 [17]

Retrospective

Developed (USA)

51

Infants (not further described)

Group B streptococcus

Mean 6 yr (range 3.3- 9.0 yr

Mortality & neurological sequelae

Univariate

Coma, hypotension (BP <40 mm Hg), low peripheral WBC count, low PMN, high CSF protein level

Letson et al., 1992 [32]

Retrospective

Developed (USA)

53

3.5 weeks - 30 months (mean 8 months

H. influenzae b

S. pneumoniae

Mean 35 months

Mortality & neurological sequelae

Multivariate

Seizures, male gender, low CSF glucose level

Anttila et al., 1994 [22]

Prospective

Developed (Finland)

143

Mean 30 months range 3 months - 15 yr

All

During hospitalization, at discharge and at 2 weeks, 3,6,12 months

Mortality & neurological sequelae

Univariate

Low body temperature, coma, neck rigidity, leaving supine position

Kirimi et al., 2003 [30]

Prospective

Developing

(Turkey)

48

2 months - 13 yr

all

Hospital duration

Mortality & neurological sequelae

Univariate

Fever >36-48 h after admission, coma 6-48 h after admission, anaemia, prolonged anaemia >3 days, low CSF WBC count, high CRP level, high CSF WBC count >3 days, low CRP level >3 days, antibiotic treatment

Valmari et al., 1987 [36]

Retrospective

Developed (Finland)

123 developing model

98 validation model

1 month- 14 yr

mean 30 months developing model

mean 20 months validation model

all

Mean 2 months

Mortality & neurological sequelae

Multivariate

Male sex, low CSF glucose level, low CSF WBC count, otitis media, low Hb, low serum potassium level, positive CSF gram stain, focal neurological signs, low peripheral WBC count, low CSF granulocyte %, low platelet count, neck rigidity, absence petechiae, duration of symptoms >48 h

Herson et al., 1977 [13]

Retrospective

Developed (USA)

73

6 weeks - 5 yr

H. influenzae b

Hospital duration,

Residual morbidity: 3 months - 2 yr

Mortality & neurological sequelae

Univariate

Coma, low body temperature, seizures, shock (BP <60 mm Hg), young age <12 months, low CSF WBC count, low Hb, low CSF glucose level, prolonged symptom duration

Bhat et al., 1987 [23]

Prospective

Developing (India)

256

Non neonatal (not further described)

all

Mortality & neurological sequelae

Univariate

Duration of illness prior to therapy >7 days, low body temperature, coma, associated illness, low peripheral WBC count, purulent/turbid CSF appearance, high CSF WBC count, high CSF protein level, low CSF glucose level, neck rigidity, distension of abdomen, no meningeal signs, positive gram stain, positive culture, type of causative pathogen