Summary: Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid offers an unbiased, broad-spectrum approach to identify infectious and autoimmune causes of meningitis and encephalitis.
mNGS - How to Get An Unbiased Approach to Meningitis and Encephalitis Diagnosis
Why This Matters:
- Central Nervous System (CNS) infections and autoimmune encephalitis are challenging to diagnose with traditional culture- or PCR-based tests due to limited pathogen coverage, slow turnaround, and nonspecific clinical presentation.
- mNGS can detect DNA and RNA pathogens simultaneously without prior assumptions about the causative agent, providing a more comprehensive diagnostic tool.
- Early implementation could reduce the need for repeated lumbar punctures and extensive microbiological testing, streamlining patient management and resource utilization.
- While modeling studies indicate promise, real-world implementation must consider test sensitivity, specificity, costs, and clinician decision-making pathways.
Key Findings:
- Diagnostic yield: Although the sample size was small, modeling predicts high positive predictive values (PPV) for DNA viruses (N = 23; 0.984 PPV), RNA viruses (0.895 PPV), bacteria (N = 16; 0.974 PPV), and fungi (N = 7; 0.928 PPV), and parasites (N = 3; 0.846 PPV) and a high negative predictive value (N = 29; 0.984) for autoimmune encephalitis when mNGS is applied early. Bayes’ theorem was used to model the probability that a patient has infection vs autoimmune encephalitis based on negative mNGS outcomes. 1
- Procedural impact: Early mNGS could prevent multiple lumbar punctures and reduce the number of redundant microbiology tests per patient.
- Time savings: Modeled use shows potential reduction in days to pathogen identification or rule-out, allowing faster initiation or de-escalation of empirical therapy.
- Complementary role: mNGS was most effective when integrated with conventional diagnostic workflows, supporting rather than replacing clinician-driven testing algorithms.
Bigger Picture: Metagenomic sequencing represents a paradigm shift in CNS diagnostics, moving from pathogen-specific tests toward unbiased, comprehensive detection. By reducing delays, minimizing invasive procedures, and guiding timely therapy, broad application of mNGS could improve patient outcomes and healthcare efficiency. As clinical validation and regulatory pathways advance, mNGS has the potential to become a core component of CNS infection and autoimmune encephalitis management, bridging molecular diagnostics with precision medicine in neurology and infectious disease care.
(Image Credit: iStock/ Rasi Bhadramani)
References:
- Vallejos et al., 2025. Evaluating the Clinical Impact of Metagenomic Next-Generation Sequencing in CNS Infections: A Diagnostic Pathway and Resource Utilization Modeling Study. Open Forum Infectious Diseases.
