This conference presents two neurologic infectious disease cases: The first involves a patient with multiple sclerosis on cladribine who developed subacute meningial symptoms with a lymphocytic meningitis, pachymeningeal and cranial nerve enhancement, and a positive Lyme evaluation. A key teaching point is that early treatment with cefdinir may have partially treated neuroborreliosis. The second case involves an older woman with cirrhosis and altered mental status initially attributed to an abdominal process, later found to have hydrocephalus, meningitis, and ventriculitis.
The teaching portion uses these cases to frame how clinicians should think about molecular diagnostics in CNS infection. It compares targeted PCR, multiplex PCR, broad-range PCR, and metagenomic next-generation sequencing, then reviews where mNGS can add value, including diagnostically difficult meningoencephalitis cases and situations where conventional testing is unrevealing. The final section emphasizes limitations of CSF mNGS: the pathogen’s nucleic acid must be present in CSF, detection does not prove causality, specimen handling matters, anatomic compartmentalization can produce false negatives, and low organism burden or high host background can reduce sensitivity.