Meningitis: Diagnosis and Management

Introduction

Meningitis is inflammation of the meninges - the pia, arachnoid and dura mater surrounding the brain and spinal cord - most often caused by infection.¹ Bacterial meningitis is a medical emergency with substantial mortality and morbidity if treatment is delayed, while viral meningitis is generally self-limiting and managed supportively. Distinguishing the two, and never letting investigation delay empirical treatment when bacterial meningitis is suspected, is the single most important principle in this topic.

Meningitis is intensively examined because it combines pattern recognition, a genuine 'never delay treatment' emergency, and public health responsibilities (notification, contact prophylaxis) that are distinctive to this condition.

Bacterial meningitis remains uncommon in the UK following the introduction of effective vaccination, with an incidence of around 1-2 per 100,000 per year in adults, but case fatality remains high and a substantial proportion of survivors have long-term sequelae. Viral meningitis is considerably more common and generally benign. The clinical task is therefore to identify the small number of bacterial cases quickly within a much larger group presenting with similar early symptoms - which is why the pathway favours immediate empirical treatment over diagnostic precision.

Aetiology

Bacterial

• Neisseria meningitidis (meningococcus) - the commonest cause in older children and young adults in the UK; classically associated with a non-blanching purpuric rash from meningococcal septicaemia
• Streptococcus pneumoniae (pneumococcus) - the commonest cause in adults overall, particularly older adults, and associated with a higher risk of neurological complications and death
• Listeria monocytogenes - important in neonates, adults over 50, pregnant women, and the immunocompromised; requires specific antibiotic cover (amoxicillin/ampicillin) not provided by cephalosporins alone
• Group B Streptococcus and Escherichia coli - the leading causes in neonates
• Haemophilus influenzae type b - now rare in the UK because of routine Hib vaccination
• Mycobacterium tuberculosis - a more insidious, subacute presentation, important in relevant epidemiological contexts or immunosuppression

Viral (the commonest overall cause of meningitis)

• Enteroviruses - the commonest viral cause
• Herpes simplex virus, varicella zoster virus
• Mumps - now rare with MMR vaccination

Other

• Fungal (e.g. Cryptococcus) - principally in the immunocompromised, particularly advanced HIV
• Non-infective - drug-induced (certain NSAIDs, IVIG), malignant (leptomeningeal metastasis), autoimmune (e.g. associated with sarcoidosis or Behçet disease)

Risk factors

• Extremes of age (infants and older adults)
• Immunosuppression (including asplenia/hyposplenism, HIV, chemotherapy)
• Unvaccinated status (Hib, meningococcal, pneumococcal vaccines)
• Close-contact living environments - university halls of residence, military barracks
• Basal skull fracture or CSF leak, providing a route for bacterial entry
• Cochlear implants and other CNS/skull base hardware
• Recent neurosurgery
• Contact with a case of meningococcal disease

Clinical features

The classic triad of fever, neck stiffness and altered mental status is present together in only a minority of confirmed cases, so its absence must never be used to rule out the diagnosis, particularly in infants and older adults where presentation is often atypical.

• Fever
• Headache, often severe
• Neck stiffness (meningism), photophobia
• Altered mental status - ranging from mild confusion to coma
• Non-blanching petechial or purpuric rash - suggests meningococcal septicaemia; a marker of severity and a specific pathogen, not a requirement for the diagnosis of meningitis itself
• Nausea and vomiting
• Seizures
• Kernig's sign (pain/resistance on extending the knee with the hip flexed) and Brudzinski's sign (involuntary hip flexion on passive neck flexion) - classic but insensitive; their absence does not exclude meningitis
• In infants: the classic signs are frequently absent or subtle - instead look for fever or hypothermia, poor feeding, irritability or lethargy, a bulging fontanelle, high-pitched cry, and hypotonia
• In older adults: presentation can be dominated by confusion alone, without prominent fever or classic meningism

Clinical examination

• Vital signs - fever, tachycardia, hypotension (signs of sepsis/septic shock)
• Glasgow Coma Scale
• Neck stiffness, Kernig's and Brudzinski's signs
• Full skin examination for a non-blanching rash, checking areas that are easy to miss (soles, palms, conjunctivae)
• Fundoscopy - for papilloedema, which should prompt caution before lumbar puncture
• Focal neurological signs - may indicate a complication such as venous sinus thrombosis, abscess, or raised intracranial pressure
• Signs of a source - ear, sinus or respiratory infection, or a CSF leak

Differential diagnosis

• Encephalitis - more prominent altered behaviour, seizures and focal deficit than isolated meningitis, reflecting brain parenchymal involvement (often overlaps as meningoencephalitis)
• Subarachnoid haemorrhage - thunderclap headache, meningism, but afebrile (unless a late complication) and of sudden onset
• Sepsis from another source with associated meningism from systemic illness, without true CNS infection
• Migraine - can cause severe headache with photophobia, but with a typical prior history and no fever or true meningism
• Drug-induced aseptic meningitis - certain NSAIDs, IVIG, some antibiotics

Investigations

• Blood cultures - before antibiotics if possible, without delaying treatment
• Blood tests: FBC, CRP, U&Es, glucose (for comparison with CSF glucose), clotting, lactate, meningococcal/pneumococcal PCR
• Lumbar puncture - the key diagnostic test where safe to perform, for CSF microscopy, culture, protein, glucose (paired with plasma glucose) and PCR
• CT head before lumbar puncture - only if there are specific concerns (reduced GCS, focal neurological signs, papilloedema, seizures, or immunocompromise) that raise the risk of coning from raised intracranial pressure; a normal CT does not guarantee lumbar puncture is safe, and clinical judgement remains essential
• Throat swab for meningococcal culture if clinically indicated

Management

Pre-hospital and immediate management

If meningococcal disease is suspected in the community (particularly with a non-blanching rash), give IM or IV benzylpenicillin (or an alternative such as ceftriaxone) immediately before transfer to hospital, unless this would cause a significant delay in transfer or there is a genuine, clearly documented allergy.

Empirical antibiotics in hospital

Adjunctive treatment

• Dexamethasone - given with or shortly before the first dose of antibiotics (not significantly after) in suspected or confirmed bacterial meningitis in adults and children beyond the neonatal period, since it reduces the risk of neurological complications, particularly hearing loss; stopped if the diagnosis turns out to be meningococcal disease without meningitis, or if the causative organism does not support ongoing benefit
• Aciclovir - added empirically if there is any possibility of herpes simplex encephalitis alongside meningitis, pending investigation results
• Fluid resuscitation and sepsis management - for haemodynamic instability, following standard sepsis pathways
• Seizure management as required
• De-escalation of antibiotics once the causative organism and sensitivities are known

Viral meningitis

Generally managed supportively - analgesia, antiemetics, and fluids - once bacterial meningitis has been excluded or empirical antibiotics have been safely stopped, since it is usually self-limiting.

Deciding when antibiotics can be stopped is a common practical dilemma. A patient improving clinically, with a lymphocytic CSF, normal glucose and negative bacterial cultures and PCR at 48 hours, has viral meningitis and antibiotics can be discontinued. Where the picture is genuinely equivocal - particularly if antibiotics were given before the lumbar puncture - it is safer to complete a bacterial course than to stop early on uncertain grounds.

Duration of treatment for confirmed bacterial meningitis is organism-dependent: typically around 7 days for meningococcus, 10-14 days for pneumococcus, and 21 days for Listeria, which is another practical reason why establishing the organism through PCR matters even when cultures have been sterilised.

Public health

Complications

• Sensorineural hearing loss - the commonest long-term neurological complication of bacterial meningitis; formal audiology assessment is recommended after recovery
• Seizures and epilepsy
• Hydrocephalus
• Focal neurological deficit, including cranial nerve palsies
• Cognitive impairment, particularly after pneumococcal meningitis
• Septic shock, disseminated intravascular coagulation, and limb ischaemia/loss in severe meningococcal septicaemia (Waterhouse-Friderichsen syndrome - adrenal haemorrhage - in fulminant cases)
• Death - mortality is substantially higher with pneumococcal than meningococcal meningitis

Red flags

Prognosis

Viral meningitis generally has an excellent prognosis with full recovery in the great majority of patients. Bacterial meningitis carries significant mortality and morbidity even with prompt treatment - pneumococcal meningitis in particular carries a higher mortality and higher rate of neurological sequelae than meningococcal meningitis. Early recognition and immediate empirical antibiotic treatment, before confirmatory investigations, is the single greatest determinant of outcome³, and formal audiology follow-up is recommended for all survivors of bacterial meningitis given the risk of hearing loss.

A point that causes real confusion in practice is the effect of prior antibiotics on the diagnosis. Giving antibiotics before lumbar puncture - which is correct, and should never be delayed - reduces the yield of CSF culture, sometimes sterilising the sample within hours. It does not, however, abolish the diagnosis: CSF white cell count, protein and glucose remain abnormal for considerably longer, and PCR for meningococcus and pneumococcus, on both blood and CSF, remains positive after cultures have become negative. The correct sequence is therefore always antibiotics first, investigations second, with PCR relied upon to establish the organism afterwards.

Recognition in primary care deserves separate emphasis. Early meningococcal disease can look indistinguishable from a viral illness, and the classic features frequently appear late. Features that should prompt urgent admission even before a rash appears include leg pain, cold hands and feet, and abnormal skin colour or mottling, which in children commonly precede the rash and reduced consciousness by several hours.

Vaccination has substantially changed the epidemiology and is worth knowing. Routine UK immunisation now includes MenB and MenC-containing vaccines in infancy, MenACWY in adolescence, and pneumococcal and Hib vaccines in the childhood schedule - which is why Hib meningitis has become rare and why serogroup C disease has largely disappeared. Additional vaccination and lifelong prophylactic antibiotics are recommended for patients with asplenia or hyposplenism and for those with complement deficiency, who are at markedly increased risk of meningococcal disease.