The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial.

BACKGROUND: In adults with acute stroke, infections occur commonly and are associated with an unfavourable functional outcome. In the Preventive Antibiotics in Stroke Study (PASS) we aimed to establish whether or not preventive antimicrobial therapy with a third-generation cephalosporin, ceftriaxone, improves functional outcome in patients with acute stroke. METHODS: In this multicentre, randomised, open-label trial with masked endpoint assessment, patients with acute stroke were randomly assigned to intravenous ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to stroke unit care, or standard stroke unit care without preventive antimicrobial therapy; assignments were made within 24 h after symptom onset. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale and analysed by intention to treat. The primary analysis was by ordinal regression of the primary outcome. Secondary outcomes included death, infection rates, antimicrobial use, and length of hospital stay. Participants and caregivers were aware of treatment allocation but assessors of outcome were masked to group assignment. This trial is registered with controlled-trials.com, number ISRCTN66140176. FINDINGS: Between July 6, 2010, and March 23, 2014, a total of 2550 patients from 30 sites in the Netherlands, including academic and non-academic medical centres, were randomly assigned to the two treatment groups: 1275 patients to ceftriaxone and 1275 patients to standard treatment (control group). 12 patients (seven in the ceftriaxone group and five in the control group) withdrew consent immediately after randomisation, leaving 2538 patients available for the intention-to-treat-analysis (1268 in the ceftriaxone group and 1270 in the control group). 2514 (99%) of 2538 patients (1257 in each group) completed 3-month follow-up. Preventive ceftriaxone did not affect the distribution of functional outcome scores on the modified Rankin Scale at 3 months (adjusted common odds ratio 0·95 [95% CI 0·82-1·09], p=0·46). Preventive ceftriaxone did not result in an increased occurrence of adverse events. Overgrowth infection with Clostridium difficile occurred in two patients (<1%) in the ceftriaxone group and none in the control group. INTERPRETATION: Preventive ceftriaxone does not improve functional outcome at 3 months in adults with acute stroke. The results of our trial do not support the use of preventive antibiotics in adults with acute stroke. FUNDING: Netherlands Organization for Health Research and Development, Netherlands Heart Foundation, and the European Research Council.

A risk score for unfavorable outcome in adults with bacterial meningitis.

OBJECTIVE: To derive and validate a bedside risk score for adverse outcome in adults with bacterial meningitis. METHODS: We derived a score for the risk for an unfavorable outcome (Glasgow Outcome Scale score 1-4) by performing logistic regression analyses of data from a prospective cohort study (Dutch Meningitis Cohort; N = 696). A key set of independent prognostic variables was selected from 22 potential predictors. A nomogram based on these key variables was constructed to facilitate use in clinical practice. To validate this nomogram, we used data from our randomized controlled trial on adjunctive dexamethasone therapy in adults with bacterial meningitis (European Dexamethasone Study; N = 301). RESULTS: Unfavorable outcome occurred in 237 of 696 episodes (34%) in the Dutch Meningitis Cohort; 143 patients (21%) died. In the analysis, 6 of 22 variables that are routinely available within 1 hour after admission were robust enough for inclusion in the final risk score: age, heart rate, Glasgow Coma Scale score, cranial nerve palsies, a cerebrospinal fluid leukocyte count less than 1,000 cells/mm3, and gram-positive cocci in cerebrospinal fluid Gram's stain. The concordance index for the risk score was 0.84 (95% confidence interval, 0.80-0.87) in the original cohort and 0.81 (95% confidence interval, 0.74-0.87) in the external validation cohort (European Dexamethasone Study). INTERPRETATION: This bedside risk score can be used to identify patients with a high risk for unfavorable outcome in adults with bacterial meningitis within 1 hour after the initial presentation.

Clinical features, outcome, and meningococcal genotype in 258 adults with meningococcal meningitis: a prospective cohort study.

Meningococcal meningitis remains a life-threatening disease. Neisseria meningitidis is the leading cause of meningitis and septicemia in young adults and is a major cause of endemic bacterial meningitis worldwide. The Meningitis Cohort Study was a Dutch nationwide prospective observational cohort study of adults with community-acquired bacterial meningitis, confirmed by culture of cerebrospinal fluid, from October 1998 to April 2002. Patients underwent a neurologic examination at discharge, and outcome was graded with the Glasgow Outcome Scale. Serogrouping, multi-locus sequence typing, and susceptibility testing of meningococcal isolates were performed. The study identified 258 episodes of meningococcal meningitis in 258 patients. The prevalence of the classical triad of fever, neck stiffness, and change in mental status was low (70/258, 27%). When rash was added to the classical triad, 229 of 258 (89%) patients had at least 2 of 4 signs. Systolic hypotension was associated with rash (22/23 vs. 137/222, p = 0.002) and absence of neck stiffness (6/23 vs. 21/220, p = 0.05). Neuroimaging before lumbar puncture was an important cause of delay of therapy: antibiotics were not initiated before computed tomography (CT) scan in 85% of patients who underwent CT scan before lumbar puncture. Unfavorable outcome occurred in 30 of 258 (12%) patients, including a mortality rate of 7%. Neurologic sequelae occurred in 28 of 238 (12%) patients, particularly hearing loss (8%). Factors associated with sepsis and infection with meningococci of clonal complex 11 (cc11) are related with unfavorable outcome.

Clinical features and prognostic factors in adults with bacterial meningitis.

BACKGROUND: We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis. METHODS: From October 1998 to April 2002, all Dutch patients with community-acquired acute bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively evaluated. All patients underwent a neurologic examination on admission and at discharge, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discharge) or favorable (a score of 5). Predictors of an unfavorable outcome were identified through logistic-regression analysis. RESULTS: We evaluated 696 episodes of community-acquired acute bacterial meningitis. The most common pathogens were Streptococcus pneumoniae (51 percent of episodes) and Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness, and a change in mental status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. On admission, 14 percent of patients were comatose and 33 percent had focal neurologic abnormalities. The overall mortality rate was 21 percent. The mortality rate was higher among patients with pneumococcal meningitis than among those with meningococcal meningitis (30 percent vs. 7 percent, P<0.001). The outcome was unfavorable in 34 percent of episodes. Risk factors for an unfavorable outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission, tachycardia, a positive blood culture, an elevated erythrocyte sedimentation rate, thrombocytopenia, and a low cerebrospinal fluid white-cell count. CONCLUSIONS: In adults presenting with community-acquired acute bacterial meningitis, the sensitivity of the classic triad of fever, neck stiffness, and altered mental status is low, but almost all present with at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. The mortality associated with bacterial meningitis remains high, and the strongest risk factors for an unfavorable outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S. pneumoniae.

Cognitive outcome in adults after bacterial meningitis.

OBJECTIVE: To evaluate cognitive outcome in adult survivors of bacterial meningitis. METHODS: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls. RESULTS: Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p<0.001) and tended to be cognitively slower than survivors of meningococcal meningitis (p = 0.08). We found a diffuse pattern of cognitive impairment in which cognitive speed played the most important role. Cognitive performance was not related to time since meningitis; however, there was a positive association between time since meningitis and self-reported physical impairment (p<0.01). The frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar. CONCLUSIONS: Adult survivors of bacterial meningitis are at risk of cognitive impairment, which consists mainly of cognitive slowness. The loss of cognitive speed is stable over time after bacterial meningitis; however, there is a significant improvement in subjective physical impairment in the years after bacterial meningitis. The use of dexamethasone was not associated with cognitive impairment.

Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series.

BACKGROUND: Bacterial meningitis is a grave disease of high incidence, especially in less developed countries. Here, we describe its clinical presentation, spectrum of complications, prognostic factors, and outcome in adults with pneumococcal meningitis. METHODS: From October, 1998, to April, 2002, we assessed 352 episodes of community-acquired pneumococcal meningitis, confirmed by culture of cerebrospinal fluid (CSF), which occurred in patients older than 16 years. Predictors for an unfavourable outcome (Glasgow outcome scale score 1-4) were identified by logistic regression with multiple imputation techniques. FINDINGS: 245 (70%) episodes of pneumococcal meningitis were associated with an underlying disorder. Cranial CT was done for 85% of episodes and revealed underlying disorders in 17% (50/299) and meningitis-associated intracranial complications in 39% (117/299). Independent predictors for an unfavourable outcome were a low score on the Glasgow coma scale, cranial nerve palsies, a raised erythrocyte sedimentation rate, a CSF leucocyte count less than 1000 cells per mm(3), and a high CSF protein concentration on admission. Overall in-hospital mortality was 30%. Prevalence of neurological and systemic complications did not differ between patients aged younger than 60 years and those aged 60 years and older; however, systemic complications were the cause of death in 59% (32/54) of fatal episodes in patients aged 60 years and older, whereas neurological complications were the cause of death in 65% (20/31) of fatal episodes in younger patients. INTERPRETATION: Pneumococcal meningitis is associated with high mortality and morbidity rates in adults. Whereas neurological complications are the leading cause of death in younger patients, elderly patients die predominantly from systemic complications.

Pneumococcal meningitis in adults: new approaches to management and prevention.

Since the virtual eradication of meningitis due to Haemophilus influenzae type B by vaccination in the developed world, pneumococcal meningitis has become the leading cause of bacterial meningitis beyond the neonatal period. Clinical and experimental research has increased our knowledge about the pathophysiology and pathogenesis of the disease over the past decades. Despite the availability of effective antibiotics, supportive care facilities, and recent advances in adjunctive strategies-ie, adjunctive dexamethasone-mortality and morbidity rates associated with pneumococcal meningitis remain unacceptably high. Although preliminary results after the introduction of the pneumococcal conjugate vaccine are promising, the incidence of multidrug-resistant pneumococcal strains is rising worldwide. Here we discuss clinical aspects of pneumococcal meningitis in adults, with focus on pathophysiology, and stress the urgent need for adequate preventive measures and new effective treatments.

Community-acquired bacterial meningitis in older people.

OBJECTIVES: To describe clinical features of bacterial meningitis in older people. DESIGN: Cohort study. SETTING: Hospitals in the Netherlands. PARTICIPANTS: Patients aged over 16 with community-acquired bacterial meningitis, confirmed using cerebrospinal fluid culture. MEASUREMENTS: Data were collected prospectively. The cohort was dichotomized with respect to age (>or=60 vs 17-59). RESULTS: Two hundred fifty-seven of 696 episodes of community-acquired bacterial meningitis (37%) occurred in elderly patients and 439 (63%) in younger adults. Older people more often presented with the triad of fever, neck stiffness, and altered mental status than younger adults (58% vs 36%; P<.001). In older people, meningitis was due to Streptococcus pneumoniae in 176 episodes (68%). In younger adults, Neisseria meningitidis was the most common pathogen, responsible for 221 episodes (50%). Elderly patients more often developed complications than younger adults (72% vs 57%; P<.001), which resulted in a higher mortality rate (34% vs 13%; P<.001). Older people tended to die more often from cardiorespiratory failure (25% vs 11%; P=.06), whereas younger adults more often died from brain herniation (23% vs 2%; P=.004). CONCLUSION: Elderly patients with bacterial meningitis often present with classic symptoms of bacterial meningitis. Bacterial meningitis within this age group is predominantly due to S. pneumoniae and is associated with high morbidity and mortality rates. Whereas older people die frequently of cardiorespiratory failure, younger adults more often die of brain herniation.

Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis.

OBJECTIVE: To evaluate whether soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in CSF can serve as a biomarker for the presence of bacterial meningitis and outcome in patients with this disease. DESIGN: Retrospective study of diagnostic accuracy. SETTING AND PATIENTS: CSF was collected from 92 adults with community-acquired bacterial meningitis who participated in the prospective Dutch Meningitis Cohort Study; 8 patients with viral meningitis and 9 healthy control subjects. RESULTS: CSF sTREM-1 levels were higher in patients with bacterial meningitis (median 82 pg/ml, range 0-988) than in those with viral meningitis (0 pg/ml, 0-48) and controls (0 pg/ml, 0-36). The diagnostic accuracy of sTREM-1 in discriminating between patients with and without bacterial meningitis, expressed as the area under the receiver operating characteristic curve, was 0.82. At a cutoff level of 20 pg/ml the sensitivity was 0.73 and specificity 0.77. In patients with bacterial meningitis CSF sTREM-1 levels were associated with mortality (survivors, median 73 pg/ml, range 0-449 pg/ml; nonsurvivors, 15 pg/ml, 0-988). CONCLUSIONS: Measuring sTREM-1 in CSF may be a valuable new additional approach to accurately diagnose bacterial meningitis and identify patients at high risk for adverse outcome. Therefore a prospective study of sTREM-1 as a biomarker in bacterial meningitis is needed.

Dexamethasone and prognostic factors in adults with bacterial meningitis.

OBJECTIVE: To determine the effect of dexamethasone on prognostic factors in adults with bacterial meningitis. DESIGN AND SETTING: A post hoc multivariate analysis of the European Dexamethasone Study. PATIENTS AND PARTICIPANTS: Dexamethasone-treated patients in the European Dexamethasone Study. As internal validation we performed an identical analysis on patients in the placebo group. MEASUREMENTS AND RESULTS: Only focal cerebral abnormalities on admission were predictive for unfavourable outcome in patients treated with early adjunctive dexamethasone (Odds ratio 3.22; 95% confidence interval 1.11-9.35; P=0.03). Other potential prognostic factors failed to achieve statistical significance. An analysis on patients in the placebo group showed prognostic factors comparable with those found in the literature without routine use of dexamethasone. CONCLUSIONS: Routine use of dexamethasone therapy may lead towards new risk stratification in adults with bacterial meningitis.

Severe neurological complications in skeletal dysplasias: two case reports.

Skeletal dysplasias form a diverse and genetically heterogeneous group of disorders, but also share many clinical and radiographic features. We describe two illustrative cases and provide a short review of the literature on the neurological complications associated with various groups of skeletal dysplasias. These two cases illustrate that management of skeletal dysplasias requires a multidisciplinary approach, aimed at preventing or minimizing medical complications. Follow-up should include regular comprehensive neurological evaluation, as neurological complications can be severe and are often treatable if diagnosed at an early stage.

Arthritis in adults with community-acquired bacterial meningitis: a prospective cohort study.

BACKGROUND: Although the coexistence of bacterial meningitis and arthritis has been noted in several studies, it remains unclear how often both conditions occur simultaneously. METHODS: We evaluated the presence of arthritis in a prospective nationwide cohort of 696 episodes of community-acquired bacterial meningitis, confirmed by culture of cerebrospinal fluid, which occurred in patients aged >16 years. The diagnosis of arthritis was based upon the judgment of the treating physician. To identify differences between groups Fisher exact statistics and the Mann-Whitney U test were used. RESULTS: Arthritis was recorded in 48 of 696 (7%) episodes of community-acquired bacterial meningitis in adults. Joint-fluid aspirations were performed in 23 of 48 patients (48%) and joint-fluid cultures yielded bacteria in 6 of 23 patients (26%). Arthritis occurred most frequently in patients with meningococcal meningitis (12%). Of the 48 patients with bacterial meningitis and coexisting arthritis, four died (8%) and 10 (23%) had residual joint symptoms. CONCLUSION: Arthritis is a common manifestation in patients with community-acquired bacterial meningitis. Functional outcome of arthritis in bacterial meningitis is generally good because meningococcal arthritis is usually immune-mediated, and pneumococcal arthritis is generally less deforming than staphylococcal arthritis. Nevertheless, additional therapeutic measures should be considered if clinical course is complicated by arthritis. In patients with infectious arthritis prolonged antibiotic therapy is mandatory.

Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study.

BACKGROUND: A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood. METHODS: We examined the relation between CSF WBC, bacteraemia and sepsis in a prospective cohort study that included 352 episodes of pneumococcal meningitis, confirmed by CSF culture, occurring in patients aged >16 years. RESULTS: CSF WBC was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm3 (interquartile range 531-6983 per mm3) and 104 patients (33%) had a CSF WBC <1000/mm3. Patients with a CSF WBC <1000/mm3 were more likely to have an unfavourable outcome (defined as a Glasgow Outcome Scale score of 1-4) than those with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was significantly associated with blood WBC (Spearman's test 0.29), CSF protein level (0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C-reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm3 more often had a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more often developed systemic complications (cardiorespiratory failure, sepsis) than those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22, 95%CI 1.02-1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17-5.14), and a low thrombocyte count on admission (Odds ratio per 100,000/mm3 increments 0.67, 95% CI 0.47-0.97) were associated with a CSF WBC <1000/mm3. CONCLUSION: A low CSF WBC in adults with pneumococcal meningitis is related to the presence of signs of sepsis and systemic complications. Invasive pneumococcal infections should possibly be regarded as a continuum from meningitis to sepsis.

Whipple's disease presenting with neurological symptoms in an immunosuppressed patient.

We report an unusual case of Whipple's disease, which remained undiagnosed for several years in a patient being treated with immunosuppressive therapy for many years. The patient presented with a purpuric rash, neurological symptoms, lymphadenopathy and gastrointestinal symptoms. The diagnosis was made by endoscopic biopsy of the duodenum with periodic acid Schiff staining, as well as PCR testing on blood and cerebrospinal fluid. The patient was successfully treated with intravenous ceftriaxone, followed by oral co-trimoxazole for 1 year.

Community-acquired bacterial meningitis in alcoholic patients.

BACKGROUND: Alcoholism is associated with susceptibility to infectious disease, particularly bacterial pneumonia. In the present study we described characteristics in alcoholic patients with bacterial meningitis and delineate the differences with findings in non-alcoholic adults with bacterial meningitis. METHODS/PRINCIPAL FINDINGS: This was a prospective nationwide observational cohort study including patients aged >16 years who had bacterial meningitis confirmed by culture of cerebrospinal fluid (696 episodes of bacterial meningitis occurring in 671 patients). Alcoholism was present in 27 of 686 recorded episodes of bacterial meningitis (4%) and alcoholics were more often male than non-alcoholics (82% vs 48%, P = 0.001). A higher proportion of alcoholics had underlying pneumonia (41% vs 11% P<0.001). Alcoholics were more likely to have meningitis due to infection with Streptococcus pneumoniae (70% vs 50%, P = 0.01) and Listeria monocytogenes (19% vs 4%, P = 0.005), whereas Neisseria meningitidis was more common in non-alcoholic patients (39% vs 4%, P = 0.01). A large proportion of alcoholics developed complications during clinical course (82% vs 62%, as compared with non-alcoholics; P = 0.04), often cardiorespiratory failure (52% vs 28%, as compared with non-alcoholics; P = 0.01). Alcoholic patients were at risk for unfavourable outcome (67% vs 33%, as compared with non-alcoholics; P<0.001). CONCLUSIONS/SIGNIFICANCE: Alcoholic patients are at high risk for complications resulting in high morbidity and mortality. They are especially at risk for cardiorespiratory failure due to underlying pneumonia, and therefore, aggressive supportive care may be crucial in the treatment of these patients.

Ataxia associated with an interhemispheric subdural hematoma: a case report.

Interhemispheric subdural hematomas are uncommon lesions. This case report describes a 77-year-old woman using anticoagulants who suddenly developed headache and ataxia of both legs. Computed tomography of the brain revealed an interhemispheric subdural hematoma, which was treated conservatively. Interhemispheric subdural hematomas should be considered in patients, especially in those using anticoagulants, even in the absence of trauma.

Nonconvulsive status epilepticus manifesting as bradyphrenia: a case report.

Generalised convulsive status epilepticus continues to be a medical emergency with high morbidity and mortality. The patient with convulsive status epilepticus has continuous or rapidly repeating seizures. In contrast, symptoms in nonconvulsive status epilepticus are often more subtle which frequently delays the diagnosis. This case describes a 27 year-old man who presented after a first seizure and only displayed symptoms of slight bradyphrenia. An electroencephalogram revealed a generalised status epilepticus. As nonconvulsive status epilepticus may clinically display only subtle symptoms a high index of suspicion is needed to initiate electroencephalographic studies.

Bacterial meningitis: a review of effective pharmacotherapy.

Acute bacterial meningitis is a serious and life-threatening neurological infectious disease. Despite the availability of effective antibiotics, supportive care facilities and recent advances in adjunctive strategies, for example, adjunctive dexamethasone, mortality and morbidity rates associated with bacterial meningitis remain unacceptably high. The review presents a brief overview of key clinical and epidemiological aspects of the disease and focuses on advances in pharmacotherapeutic strategies in adult patients with bacterial meningitis in the developed world.

Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis.

OBJECTIVES: This study investigated levels of coagulation and fibrinolysis factors in cerebrospinal fluid (CSF) from adults with bacterial meningitis in relation to development of brain infarction. METHODS: CSF was collected from 92 adults with community-acquired bacterial meningitis, who participated in the prospective Dutch Meningitis Cohort Study; 8 patients with viral meningitis and 9 healthy control subjects. Levels of proteins involved in the coagulation cascade were determined by means of immunoassays. RESULTS: Bacterial meningitis was accompanied by local activation of coagulation, as shown by significantly higher CSF soluble tissue factor (P<0.001) and prothrombin fragment F1+2 concentrations (P<0.001) as compared to viral meningitis patients and controls. This was accompanied by a significantly higher D-dimer formation (P<0.001). In addition, in bacterial meningitis fibrinolysis was attenuated, since CSF plasminogen activator inhibitor (PAI)-1 levels were significantly higher as compared to the controls (P=0.02). In patients with bacterial meningitis who developed brain infarction, CSF PAI-1 levels were higher than in those without infarction (P=0.04). CONCLUSIONS: Activation of coagulation and attenuation of fibrinolysis in the CSF are important features of bacterial meningitis; the net effect on fibrin turnover may contribute to the development of brain infarction.

Cognitive outcome in adults with moderate disability after pneumococcal meningitis.

OBJECTIVES: To assess cognitive outcome and quality of life in patients with moderate disability after bacterial meningitis as compared to patients with good recovery. METHODS: Neuropsychological evaluation was performed in 40 adults after pneumococcal meningitis; 20 patients with moderate disability at discharge on the glasgow outcome scale (GOS score 4) and 20 with good recovery (GOS score 5). RESULTS: Patients with GOS score 4 had similar test results as compared to patients with GOS score 5 for the neuropsychological domains 'intelligence', 'memory' and 'attention and executive functioning'. Patients with GOS score 4 showed less cognitive slowness than patients with GOS score 5. In a linear regression analysis cognitive speed was related to current intelligence, years of education and time since meningitis. Overall performance on the speed composite score correlated significantly with time since meningitis (-0.62; P<0.001). Therefore, difference between both groups may have been related to a longer time between meningitis and testing for GOS four patients (29 vs. 12 months; P<0.001). CONCLUSIONS: Patients with moderate disability after bacterial meningitis are not at higher risk for neuropsychological abnormalities than patients with good recovery. In addition, cognitive slowness after bacterial meningitis may be reversible in time.