Differentials
Bacterial meningitis (adults)
SIGNS / SYMPTOMS
No differentiating symptoms and signs.
INVESTIGATIONS
Typical cerebrospinal fluid (CSF) in acute bacterial meningitis will show a neutrophilic pleocytosis, elevated CSF protein, and decreased CSF glucose.
Bacteria may be seen on Gram stain and may be isolated on culture of CSF or blood. An aseptic profile is seen in meningitis due to syphilis, Lyme disease, rickettsia, and brucellosis.
Bacterial meningitis (children)
SIGNS / SYMPTOMS
No differentiating symptoms and signs.
INVESTIGATIONS
Typical CSF in acute bacterial meningitis will show a leukocytosis, elevated CSF protein, and low CSF:blood glucose ratio.
Bacteria may be seen on Gram stain and may be isolated on culture of CSF or blood. An aseptic profile is seen in meningitis due to syphilis, Lyme disease, rickettsia, and brucellosis.
Encephalitis
SIGNS / SYMPTOMS
Patients with viral meningitis have normal cerebral function. Abnormal cerebral function such as altered behaviour, or speech or motor disorders, particularly when seen in association with fever, suggests a diagnosis of encephalitis.
INVESTIGATIONS
Encephalitis is a clinical diagnosis. The CSF profile will be similar to that seen in viral meningitis but the aetiological agents are sometimes different.
Encephalopathy (toxic/metabolic)
SIGNS / SYMPTOMS
A multitude of metabolic factors and remote infections can cause brain parenchymal dysfunction without structural damage to the brain.
Frequently encountered in hospital/nursing-home settings.
Patients with viral meningitis have normal cerebral function. Altered mental status and focal neurological signs can be seen in people with encephalopathy due to metabolic factors or infection outside the nervous system.
INVESTIGATIONS
Normal CSF analysis, normal MRI, electroencephalogram (EEG) diffuse slowing, triphasic waves.
Other intracranial pathology
SIGNS / SYMPTOMS
Patients with other intracranial pathology, such as a subarachnoid haemorrhage (SAH), may also present with acute onset of neck stiffness, headache, and photophobia (but will not have an associated rash or fever).
INVESTIGATIONS
Intracranial pathology may be evident on imaging (e.g., CT head scan positive: the presence of the hyperdense appearance of blood in the subarachnoid space/basal cisterns confirms SAH).
Drug-induced meningitis
SIGNS / SYMPTOMS
No differentiating symptoms and signs.
NSAIDs, trimethoprim/sulfamethoxazole, amoxicillin, ranitidine, immune checkpoint inhibitors are potential culprit drugs.[69][70]
INVESTIGATIONS
This is a diagnosis of exclusion. CSF typically shows a neutrophilic pleocytosis. Symptoms resolve once the offending drug is stopped.
Tuberculous meningitis
SIGNS / SYMPTOMS
Presentation is usually more chronic with a prodromal period of general malaise and fever preceding meningitis.
INVESTIGATIONS
Presents with a lymphocytic pleocytosis.
CSF protein is usually markedly elevated; CSF glucose is depressed.
Diagnosis rests on positive microscopy or culture.
Chest x-ray may be abnormal.
Cryptococcal meningitis
SIGNS / SYMPTOMS
Presentation is often insidious with onset of headache and fever over weeks or months. A rash resembling molluscum contagiosum may be present in disseminated cryptococcal disease.
INVESTIGATIONS
Testing CSF for cryptococcal antigen has a sensitivity of almost 100% for cryptococcal meningitis.
In HIV-positive patients the fungal burden is high, leading to high CSF pressures. The CSF leukocyte count may be low. An India ink stain or cryptococcal antigen is usually positive.
HIV-negative patients have higher CSF leukocyte counts and the India ink stain is positive in only half of cases.
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