Meningitis and encephalitis (emergency department diagnosis and management)

Acute central nervous system infection sits on the time-critical edge of emergency medicine: a few hours of delay converts a treatable meningitis into a death or a devastating neurological injury. The Fellowship candidate must recognise the clinical triad, give the empiric regimen without waiting for imaging, interpret the cerebrospinal fluid by its cell count and glucose, and add aciclovir the moment herpes simplex encephalitis enters the differential. Two diseases dominate the workload — bacterial meningitis (pneumococcal, meningococcal, listerial) and herpes simplex encephalitis — and both are managed on probability, not on proof.[1][2]

Definition and classification

Meningitis is inflammation of the meninges lining the brain and spinal cord; encephalitis is inflammation of the brain parenchyma itself, and the two overlap clinically as meningoencephalitis. The decisive split is bacterial versus viral, because bacterial meningitis is destroyed by an hour of the right antibiotic and viral meningitis is largely supportive. Encephalitis is most often viral, and herpes simplex virus type 1 is the treatable, exam-critical cause. Fungal meningitis (cryptococcus) and tuberculous meningitis run a subacute course and are suspected in the immunocompromised and the endemic-risk patient. Aseptic meningitis denotes a lymphocytic CSF with a negative bacterial culture — usually viral, but also partially-treated bacterial, TB, fungal, drug-induced, or autoimmune.[4]

Pathophysiology

Bacterial meningitis begins when a colonising nasopharyngeal organism (pneumococcus, meningococcus) invades the bloodstream and seeds the choroid plexus and the meninges, or reaches the meninges by direct extension from a contiguous focus (otitis media, sinusitis, mastoiditis, a skull-base fracture). Once in the subarachnoid space the bacteria multiply in a compartment that lacks complement and antibody, generating an intense neutrophilic exudate. The inflammatory cascade increases blood–brain barrier permeability, raises CSF protein, consumes glucose, and produces cerebral oedema; the raised intracranial pressure is the mechanism of both the headache and the lethal complication of herniation. Herpes simplex encephalitis is different: the virus reaches the temporal lobe by the olfactory or trigeminal pathway and causes haemorrhagic, necrotising inflammation — typically bilateral but asymmetric in the inferomedial temporal and frontal lobes.[4]

Epidemiology and risk factors

The commonest community-acquired organism in adults is Streptococcus pneumoniae, followed by Neisseria meningitidis, with Haemophilus influenzae now rare since conjugate vaccination. Listeria monocytogenes is the critical exception: it is not covered by ceftriaxone and it targets the over-50 age group, the immunocompromised, the pregnant, and the alcoholic — these patients must have ampicillin added. Risk factors that broaden the differential include asplenia and sickle-cell disease (encapsulated organisms), HIV and immunosuppression (cryptococcus, listeria, TB), a CSF shunt or recent neurosurgery (staphylococci and Gram-negatives), and uncontrolled alcohol excess (listeria and pneumococcus). Herpes simplex encephalitis is the commonest sporadic viral encephalitis at any age, with a mortality that exceeds 70 per cent untreated.[1][4][9]

Clinical presentation

The classic triad is fever, headache and neck stiffness, but all three are present together in only about 44 per cent of cases; at least two appear in roughly 95 per cent, and almost every patient has a fever with a headache. The decisive additional feature is an altered mental status — confusion, drowsiness or coma — which distinguishes encephalitis or severe bacterial meningitis from simple viral meningitis and which independently predicts a poor outcome. Meningism is elicited by neck stiffness, a positive Kernig sign (resistance to knee extension with the hip flexed), and a positive Brudzinski sign (involuntary hip flexion on neck flexion), though both are insensitive. A petechial or purpuric rash with a fever is meningococcaemia until proven otherwise and demands immediate empiric therapy. Herpes simplex encephalitis presents with fever, an altered consciousness, behavioural change, dysphasia, focal temporal-lobe seizures, or olfactory and gustatory hallucinations — a clinical pattern, not a single sign.[4]

[5]

Differential diagnosis

The febrile patient with a headache and an altered or normal consciousness generates a differential that the history, the imaging and the CSF resolve — but several mimics are time-critical in their own right.[8]

Bedside assessment

Assess and secure the airway, breathing and circulation first — a depressed Glasgow Coma Scale, particularly below 9, threatens the airway and mandates intubation. Record the GCS in its eye, verbal and motor components, examine for a petechial or purpuric rash, look for a focal neurological deficit, and search for a contiguous source (otitis media, sinusitis, mastoiditis, a CSF leak or a cochlear implant). Fundoscopy for papilloedema is recommended but is unreliable and must not delay therapy. The early task is to decide whether this is septic shock (manage with the Hour-1 sepsis bundle) or a stable patient suitable for an urgent lumbar puncture after blood cultures.[4]

Investigations

The cerebrospinal fluid is the diagnostic centrepiece, but it is never allowed to delay the antibiotic. Blood cultures are drawn first (positive in around half of bacterial meningitis), then a coagulation screen and full blood count (the platelet count and INR screen for the disseminated intravascular coagulation of meningococcaemia). A serum glucose is taken with the LP so the CSF-to-serum ratio can be calculated. The CT before the LP is reserved for the high-risk patient (see below); a normal CT does not guarantee a safe LP. For suspected HSV, the CSF HSV polymerase chain reaction is highly sensitive but can be negative in the first 48 hours, so a negative PCR with a compatible picture warrants a repeat at three to seven days and empirical aciclovir in the meantime. A CT or MRI head with contrast and an electroencephalogram support the diagnosis of HSV encephalitis when the temporal-lobe picture is clear.[8]

[8]

CSF interpretation — bacterial versus viral versus tuberculous

The CSF cell count, differential, protein and glucose resolve the aetiology. A traumatic tap is corrected by subtracting one white cell for every 700 red cells, and the CSF glucose is always interpreted against a simultaneous serum glucose.[1]

[1]

A neutrophil-predominant pleocytosis with a low glucose and a high protein is bacterial until proven otherwise; a lymphocytic picture with a normal glucose is viral, TB (low glucose) or fungal; a frankly normal CSF with a strong clinical story does not exclude early bacterial meningitis or HSV encephalitis and the empiric therapy continues.[1]

Immediate management and resuscitation

Stabilise the airway, give oxygen, establish intravenous access and treat shock with fluid boluses and vasopressors by the sepsis pathway. Draw blood cultures, then give the first dose of the empiric regimen immediately — within the first hour — and before the lumbar puncture whenever the LP will be delayed. Dexamethasone 10 mg intravenously is given just before or with the first antibiotic dose when pneumococcal meningitis is suspected, because the steroid blunts the inflammatory surge released by antibiotic-mediated bacterial lysis. If the LP cannot be performed within an hour, the antibiotic and the steroid are given regardless; the CSF is then obtained when practical, accepting a lower culture yield.[8]

[8]

Definitive management and the antiviral

Once the organism is identified, therapy is narrowed. Pneumococcal meningitis receives ceftriaxone 2 g every 12 hours (with vancomycin until sensitivity confirms penicillin susceptibility), meningococcal meningitis receives ceftriaxone 2 g every 12 hours for seven days, and listerial meningitis receives ampicillin or amoxicillin plus gentamicin for at least three weeks. Herpes simplex encephalitis receives aciclovir 10 mg/kg intravenously every 8 hours for 14 to 21 days, with hydration to protect against the nephrotoxicity; the dose is weight-based and the course is long because relapse follows an abbreviated course. Tuberculous meningitis is treated with quadruple therapy (rifampicin, isoniazid, pyrazinamide, ethambutol) plus adjunctive corticosteroids, and cryptococcal meningitis with amphotericin B plus flucytosine induction then fluconazole consolidation. Chemoprophylaxis of the close contacts of a meningococcal case — rifampicin 600 mg every 12 hours for two days, or a single oral dose of ciprofloxacin 500 mg — is a public-health responsibility that begins from the emergency department.[4]

Subtypes and specific scenarios

Meningococcaemia progresses within hours from a febrile flu-like illness to a purpuric rash, septicaemic shock and multi-organ failure; the Waterhouse-Friderichsen syndrome is the bilateral adrenal haemorrhage of disseminated intravascular coagulation that drives the refractory shock. Herpes simplex encephalitis is the time-critical, treatable encephalitis — the clinical pattern is temporal-lobe, the MRI shows oedema in the inferomedial temporal lobe, and the CSF HSV PCR is the diagnostic test. Tuberculous meningitis runs a basal, vasculitic course with cranial-nerve palsies and a very low CSF glucose. Cryptococcal meningitis complicates advanced HIV with an insidious headache and a raised opening pressure. Post-neurosurgical or shunt-related meningitis is caused by staphylococci and Gram-negative bacilli and demands vancomycin plus a cephalosporin or meropenem with Gram-negative cover.[4]

Complications and pitfalls

The complications are systemic and neurological. Cerebral oedema and raised intracranial pressure progress to tentorial herniation — the feared complication of a lumbar puncture performed against a raised pressure, which the CT-before-LP criteria exist to prevent. Seizures may be generalised or focal and require standard anticonvulsants. Disseminated intravascular coagulation accompanies meningococcaemia and drives the purpura, the adrenal haemorrhage and the digital ischaemia. Waterhouse-Friderichsen syndrome is the adrenal failure of that haemorrhage and demands stress-dose hydrocortisone in the shocked patient. Long-term sequelae include sensorineural deafness, cognitive impairment, epilepsy and hydrocephalus. The pitfalls are the dangerous inverse of the management: delaying the antibiotic for the CT or the LP; omitting dexamethasone or giving it after the antibiotic; forgetting ampicillin for listeria in the over-50; failing to start aciclovir empirically in suspected HSV; performing an LP against a raised pressure; and forgetting chemoprophylaxis and public-health notification.[8]

Prognosis and disposition

Community-acquired bacterial meningitis carries an in-hospital mortality around 20 per cent, and a further 30 per cent survive with neurological sequelae; pneumococcal disease and an altered consciousness at presentation are the worst prognostic markers. Herpes simplex encephalitis kills around 70 per cent of untreated patients and, even with aciclovir, leaves roughly 30 per cent dead or severely disabled — the outcome tracks the time to the antiviral. Disposition is to a ward bed for the stable patient with a normal GCS, and to intensive care for any patient with a GCS of 8 or below, recurrent seizures, respiratory failure, or septic shock. Public-health notification of a confirmed or suspected meningococcal case is mandatory and triggers contact tracing and chemoprophylaxis.[9]

Special populations

The neonate presents with non-specific signs (lethargy, poor feeding, a bulging fontanelle, apnoea) and the organisms are group B streptococcus, Escherichia coli and Listeria; the empiric regimen is ampicillin plus a third-generation cephalosporin (or ampicillin plus gentamicin). The elderly and the immunocompromised present atypically — confusion without fever, or a subtle meningeal sign — and mandate ampicillin for listeria on top of the standard regimen. The pregnant patient has a heightened listeria risk and receives ampicillin; aciclovir is safe in pregnancy and is not withheld. The asplenic patient is at extreme risk of overwhelming pneumococcal or meningococcal sepsis and receives ceftriaxone empirically at any febrile presentation. The post-neurosurgical or shunt patient has a different flora and a different regimen, focused on staphylococci and Gram-negatives.[8]

The empiric regimen in detail

The empiric regimen is the single most exam-critical therapeutic decision in central nervous system infection, and it is built from three questions: which organism, which host, and which syndrome (meningitis versus encephalitis). The backbone is a third-generation cephalosporin (ceftriaxone or cefotaxime) at meningitic dosing; vancomycin is added for the penicillin-resistant pneumococcus; ampicillin is added for listeria in the at-risk host; and aciclovir is added the moment herpes encephalitis is plausible. The mnemonic below fixes the agent and the dose in memory.[1][2][7]

[8] [5]

Organism-specific definitive therapy

Once the organism and the sensitivities return, the regimen narrows. The table below fixes the agent, the dose, and the duration for each of the common pathogens — the duration matters because an abbreviated course of aciclovir or of listerial therapy relapses.[4]

[4]

The role of dexamethasone

Adjunctive dexamethasone blunts the inflammatory cytokine surge released by the antibiotic-mediated bacterial lysis. The benefit is real but narrow: it reduces the neurological sequelae and, in pneumococcal disease, the mortality, but ONLY when it is given before or with the first antibiotic dose — given after the antibiotic it is ineffective because the inflammatory cascade has already been triggered. The Cochrane meta-analysis confirmed the mortality benefit in pneumococcal meningitis and the hearing-loss reduction in Haemophilus disease.[3][5][6] The trial that established the practice — the European Dexamethasone in Adulthood Bacterial Meningitis Study — showed a reduction in the unfavourable outcome from 25 per cent to 15 per cent in pneumococcal meningitis, with the benefit disappearing when the steroid was given after the antibiotic.[5]

[5]

Lumbar puncture timing and technique

The lumbar puncture is the diagnostic centrepiece, but its timing is governed by one overriding principle: the antibiotic is never delayed for the LP or for the CT. If the LP cannot be performed within an hour, the empiric regimen is given regardless, and the LP follows when practical — accepting that the Gram-stain and culture yields fall after antibiotics, but the cell count, the protein, the glucose ratio, and the HSV PCR remain informative for days. The CSF bacterial culture is rendered sterile within 4 to 8 hours of an effective antibiotic dose, but the white-cell differential and the biochemistry are preserved.[8]

When to CT before the LP

The CT-before-LP criteria exist to prevent the cerebral herniation — the feared, often fatal complication of performing an LP against a raised intracranial pressure from a space-occupying lesion or a cerebral oedema. The six criteria are drawn from the IDSA and the ESCMID frameworks.[7][2] A normal CT does NOT guarantee a safe LP, but the absence of all six criteria in an immunocompetent patient with a normal GCS and no focal deficit makes the LP safe to proceed without imaging.

[8]

CSF opening pressure and the Gram stain

The opening pressure is measured only in the lateral decubitus position with the legs relaxed — a normal adult pressure is 8 to 20 cm of water, and a raised pressure above 25 cm is characteristic of the acute bacterial meningitis, the cryptococcal meningitis, and any space-occupying lesion. The CSF is interpreted by its cell count and differential, its glucose against a simultaneous serum glucose, and its protein — the Gram stain and the culture are confirmatory but rarely available in the first hour. A traumatic tap is corrected by subtracting one white cell for every 700 red cells.[2]

[9]

Chemoprophylaxis and public health

The meningococcal disease is notifiable in every jurisdiction, and the chemoprophylaxis of the close contacts is a public-health responsibility that begins in the emergency department. The contacts at risk are the household and the kissing contacts, the healthcare worker who performed the mouth-to-mouth resuscitation or who was exposed to the droplets during an intubation without protection, and the index case themselves before discharge (to eradicate the nasopharyngeal carriage). The window is short — the chemoprophylaxis is most effective within 24 hours of the index case's diagnosis and is generally not recommended after 7 days.[2]

[9] [2]

Viral encephalitis in depth

The viral encephalitis is distinguished from the viral meningitis by the involvement of the brain parenchyma — an altered consciousness, a seizure, a focal deficit, or a behavioural change, in addition to the fever and the headache. The herpes simplex virus type 1 is the commonest sporadic cause and the only one with a time-critical, mortality-reducing therapy, so the empiric aciclovir is started the moment the diagnosis is plausible and is continued until the CSF HSV PCR is negative at 3 to 7 days. The other viral causes — the varicella-zoster, the enterovirus, the Epstein–Barr, the mumps, and the arboviruses (the Japanese encephalitis, the Murray Valley encephalitis, the West Nile) — are managed supportively, though the aciclovir is empirically continued until the HSV is excluded because the clinical overlap is complete.[4]

[4] [4] [4]

Pitfalls at the bedside

The errors in the meningitis and the encephalitis are the inverse of the correct management, and they are the recurrent themes of the Fellowship viva and the morbidity-and-mortality meeting.[8]

[8] [8] [1] [8] [8] [1] [4] [8] [8] [8]

Evidence and regional guidelines

The contemporary framework is the ESCMID 2016 guideline on the diagnosis and treatment of acute bacterial meningitis[2] and the landmark New England Journal review of community-acquired bacterial meningitis in adults.[1] Adjunctive dexamethasone is supported by the Cochrane meta-analysis, which shows a mortality and morbidity benefit concentrated in pneumococcal disease when the steroid is given before or with the first antibiotic dose.[3] Aciclovir for herpes simplex encephalitis rests on the classic vidarabine-versus-aciclovir trial that established the mortality advantage of aciclovir.[4]

Exam pearls

• The classic triad (fever, headache, neck stiffness) is all present in only 44 per cent — fever plus headache is present in 95 per cent; an altered consciousness is the red flag for severity.
• Antibiotics before the LP, always — give the empiric dose within the first hour and before any CT if there is any delay; a normal CT does not guarantee a safe LP.
• Dexamethasone 10 mg IV before or with the first antibiotic dose, for four days — benefit is in pneumococcal disease.
• Add ampicillin (2 g IV every 4 hours) for listeria in any patient over 50, immunocompromised, pregnant, or alcoholic — ceftriaxone does not cover it.
• Aciclovir 10 mg/kg IV every 8 hours for suspected HSV — start empirically, do not wait for the PCR.
• CSF: neutrophils and low glucose means bacterial; lymphocytes and normal glucose means viral; lymphocytes and very low glucose means tuberculous.
• Chemoprophylaxis for meningococcal contacts: rifampicin 600 mg twice daily for two days, or a single dose of ciprofloxacin 500 mg — and notify public health.
• S. pneumoniae is the commonest community-acquired organism in adults (around 68 per cent), followed by N. meningitidis (11 per cent); Listeria targets the over-50 and the immunocompromised and is not covered by any cephalosporin.
• The CSF Gram stain is positive in 60 to 90 per cent of untreated bacterial meningitis and becomes negative within hours of the first antibiotic dose — send the CSF early.
• The CSF bacterial culture is sterilised within 4 to 8 hours of an effective antibiotic, but the cell count, the glucose, the protein and the HSV PCR remain informative — never withhold the antibiotic for the LP.
• The opening pressure is measured only in the lateral decubitus position — a normal adult range is 8 to 20 cm of water; a raised pressure is typical of bacterial and of cryptococcal meningitis.
• A traumatic tap is corrected by subtracting one white cell for every 700 red cells, and the CSF glucose is always interpreted against a simultaneous serum glucose (a ratio below 0.4 favours bacterial).
• The CSF lactate (above 4 mmol/L bacterial, below 3 mmol/L viral) is a useful adjunct in the ambiguous or the partially-treated CSF.
• The dexamethasone is futile if given after the antibiotic — the inflammatory cascade from the bacterial lysis is already running; give it before or with the first dose.
• The CSF HSV PCR can be negative in the first 48 hours — a compatible picture with a negative early PCR warrants a continued aciclovir and a repeat LP at 3 to 7 days.
• Aciclovir is crystalline-nephrotoxic — pre-hydrate with a litre of normal saline and dose-adjust for the renal function; the 14 to 21-day course must not be truncated (the relapse follows an abbreviated course).
• Tuberculous meningitis is the great mimic of the subacute case — a lymphocytic CSF, a very high protein, and a glucose often below 1 mmol/L; treat empirically on the suspicion and do not wait for the culture.
• Cryptococcal meningitis in the CD4-below-100 patient may have a bland CSF — the India ink, the cryptococcal antigen, and the opening pressure are the keys; a raised pressure is decompressed by the repeated therapeutic LPs.
• The neonate has non-specific signs and a different flora (the group B strep, the E. coli, the Listeria) — the empiric regimen is ampicillin plus a third-generation cephalosporin or plus gentamicin.
• Meningococcaemia may present with the rash before the neck stiffness — any febrile petechial or purpuric rash is treated empirically; the Waterhouse-Friderichsen adrenal haemorrhage demands the stress-dose hydrocortisone in the refractory shock.
• A normal CT does NOT guarantee a safe LP — apply the six CT-before-LP criteria, but the priority in a deteriorating patient is the intubation, the CT, and the neurosurgery, not the LP.[9]

Exam practice

[8] [4]

Red flags

[8]

References

1. [1]van de Beek D, de Gans J, Tunkel AR, Wijdicks EFM. Community-acquired bacterial meningitis in adults. New England Journal of Medicine, 2006.PMID 16394301
2. [2]van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clinical Microbiology and Infection, 2016.PMID 27062097
3. [3]Brouwer MC, McIntyre P, de Gans J, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database of Systematic Reviews, 2010.PMID 20824838
4. [4]Whitley RJ, Alford CA, Hirsch MS, et al. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. New England Journal of Medicine, 1986.PMID 3001520
5. [5]de Gans J, van de Beek D, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. New England Journal of Medicine, 2002.PMID 12432041
6. [6]Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database of Systematic Reviews, 2015.PMID 26362566
7. [7]Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clinical Infectious Diseases, 2004.PMID 15494903
8. [8]Auburtin M, Wolff M, Charpentier J, et al. Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis. Critical Care Medicine, 2006.PMID 16915106
9. [9]Drost EHGM, Schepers EN, Chekrouni N, et al. Outcomes of adults with community-acquired bacterial meningitis in the Netherlands: a prospective nationwide cohort study. Lancet Regional Health Europe, 2026.PMID 41323877