Introduction: The Dual Face of Neisseria meningitidis
Invasive meningococcal disease (IMD) remains one of the most formidable challenges in acute medicine. Despite its relatively low incidence in developed nations due to successful vaccination programs, the infection caused by Neisseria meningitidis continues to be associated with high morbidity and sudden mortality. For clinicians in the intensive care unit (ICU), the presentation of IMD in adults often oscillates between two clinical extremes: a predominantly neurological syndrome characterized by meningitis and a predominantly hemodynamic syndrome characterized by septic shock and purpura fulminans.
Historically, these presentations have often been conflated in retrospective analyses, yet their pathophysiology, resource requirements, and outcomes are markedly different. Understanding these phenotypes is not merely an academic exercise; it is essential for risk stratification and the optimization of emergency management protocols. The RETRO-MENINGO study, a comprehensive nationwide investigation across France, provides the most robust evidence to date regarding these distinct adult phenotypes and the factors that drive their divergent clinical courses.
The RETRO-MENINGO Study: Methodology and Scope
The RETRO-MENINGO study was a nationwide, multicenter, retrospective cohort study conducted across 102 French ICUs. The study period spanned nearly a decade, from January 1, 2016, to December 31, 2024, capturing data from 654 adult patients (aged 18 or older) with microbiologically confirmed IMD.
Patients were categorized into two cohorts based on their primary reason for ICU admission:
1. The Neurological Presentation: Characterized by central nervous system involvement, primarily meningitis.
2. The Hemodynamic Presentation: Characterized by sepsis, septic shock, and systemic cardiovascular instability.
The primary endpoint was the day-60 mortality rate. Secondary endpoints included the need for organ support (mechanical ventilation, vasopressors, renal replacement therapy) and the identification of independent risk factors for mortality.
Clinical Phenotyping: Hemodynamic vs. Neurological Presentations
Of the 654 patients included in the study, 62% (407 patients) presented with a neurological phenotype, while 38% (247 patients) presented with a hemodynamic phenotype. This distribution highlights that while meningitis is the more common reason for ICU admission in the context of meningococcal infection, a substantial minority of patients suffer from life-threatening systemic collapse.
Demographic and Microbiological Divergence
The study revealed significant differences in the patient profiles between the two groups. Patients in the hemodynamic group were generally older, with a median age of 39 years compared to 30 years in the neurological group. Furthermore, immunosuppression was significantly more prevalent in the hemodynamic cohort (17.0% vs. 7.1%).
Microbiologically, the phenotypes were driven by different serogroups. Serogroup B was the predominant driver of neurological presentations, whereas serogroup W135 was significantly more common in those with hemodynamic failure. This finding aligns with global epidemiological shifts, where the emergence of the W135 ST-11 hypervirulent lineage has been associated with more severe systemic disease and atypical presentations.
Clinical Severity and Resource Utilization
The hemodynamic phenotype was characterized by a more explosive clinical onset. These patients were admitted to the ICU significantly earlier (median of 1 day after symptom onset vs. 2 days for the neurological group) and had a higher prevalence of purpuric rash (55.9% vs. 43.7%). Bacteremia was nearly universal in the hemodynamic group (83.8%), whereas it was found in only about a third of the neurological cases (35.6%).
In terms of ICU management, the hemodynamic cohort required far more intensive organ support. They were more likely to receive vasopressors, invasive mechanical ventilation, blood product transfusions, and renal replacement therapy. This disparity in resource utilization underscores the profound systemic inflammatory response and capillary leak syndrome associated with the hemodynamic phenotype.
Prognostic Determinants and Mortality Outcomes
The most striking finding of the RETRO-MENINGO study was the massive disparity in survival. The day-60 mortality rate for the hemodynamic presentation was 25.5%, more than five times higher than the 4.7% observed in the neurological presentation.
Through multivariate analysis, several independent risk factors for day-60 mortality were identified:
1. Hemodynamic presentation at admission (aOR 4.33)
2. Age over 35 years (aOR 3.65)
3. Arterial lactate levels exceeding 5 mmol/L (aOR 2.60)
4. Absence of comorbidities (aOR 2.21)—a finding that may reflect a more aggressive immune response in previously healthy individuals.
5. Rapid symptom onset of less than 24 hours (aOR 1.90)
Conversely, the early administration of a parenteral third-generation cephalosporin (3GC) prior to ICU admission was found to be strongly protective, reducing the risk of death by nearly 70% (aOR 0.31). This highlights the “golden hour” of antibiotic therapy; every delay in the community or emergency department setting directly correlates with an increased risk of mortality.
Expert Commentary: Bridging Clinical Phenotypes and Management
The RETRO-MENINGO study clarifies that IMD is not a monolithic disease entity. The hemodynamic phenotype likely represents a state of overwhelming meningococcemia where the bacterial load and the subsequent endotoxin release trigger a catastrophic cytokine storm, endothelial dysfunction, and massive capillary leak. In contrast, the neurological phenotype represents a more localized, albeit severe, infection of the subarachnoid space.
The association of Serogroup W135 with the hemodynamic phenotype is particularly concerning for public health. This serogroup has been linked to higher case-fatality rates across Europe and South America, and the RETRO-MENINGO data suggests that its propensity for causing systemic shock rather than isolated meningitis is a primary driver of this lethality.
From a clinical perspective, the study reinforces the necessity of the “purpura rule”: any patient with a febrile illness and a petechial or purpuric rash must receive immediate parenteral antibiotics before hospital transfer. The fact that early 3GC administration was the strongest modifiable protective factor emphasizes that the battle against IMD mortality is often won or lost before the patient even reaches the ICU gates.
Conclusion: Toward Phenotype-Specific Management
The RETRO-MENINGO study provides a robust framework for understanding the clinical diversity of invasive meningococcal disease in adults. By distinguishing between neurological and hemodynamic presentations, clinicians can better predict resource needs and counsel families on prognosis.
The high mortality associated with the hemodynamic phenotype, even in a modern ICU setting, serves as a sobering reminder of the virulence of Neisseria meningitidis. Future research should focus on adjunctive therapies—such as targeted anti-inflammatory agents or endothelial stabilizers—that may mitigate the catastrophic shock associated with the hemodynamic phenotype, while public health efforts must continue to emphasize the importance of broad-spectrum vaccination and rapid antibiotic intervention.
References
1. Contou D, Painvin B, Daubin D, et al. Hemodynamic and neurological presentations of invasive meningococcal disease in adults: a nationwide study across 100+ French ICUs: The RETRO-MENINGO study. Intensive Care Med. 2025 Sep;51(9):1587-1602. doi: 10.1007/s00134-025-08043-4.
