Fever And Confusion: Meningitis And Encephalitis; Suppurative Brain Infection
Fever accompanied by altered mental status can indicate meningitis (infection/inflammation of the meninges), encephalitis (infection/inflammation of the brain parenchyma), or suppurative brain infections such as cerebral abscess, which are life-threatening conditions requiring urgent diagnosis and treatment.
Fever and Confusion: Meningitis, Encephalitis, and Suppurative Brain Infections
Lecture Map
A patient presenting with fever + confusion is a neurological emergency. The core question is: Is there a CNS infection? If yes, what kind — and how do we treat it before irreversible damage occurs? This lecture teaches you a systematic clinical approach to differentiate CNS infections (meningitis, encephalitis, brain abscess) from non-CNS causes of fever with altered mental state, and covers the aetiologies, investigations (especially CSF interpretation), and management of each entity.
1) Clinical approach in patients presenting with fever and confusion 2) Common differential diagnoses in patients presenting with fever and confusion 3) Common aetiologies, clinical presentation, investigations, and management of patients with meningitis, encephalitis and brain abscess
- This is a bread-and-butter General Clerkship topic tested repeatedly in MCQ, SAQ, and minicases.
- Directly links to: GC 048 (Fever), GC 081 (Seizure/LOC/Encephalopathy), GC 101 (Diagnosis of infections), GC 106 (Practical antibiotic use), GC 111 (Raised ICP/Hydrocephalus), GC 225 (Neuroimmunological disorders), and Neurology Introduction to CNS Investigations.
- Past paper questions on CSF interpretation appear almost every year (2019 SAQ Q10, 2020 MCQ Q34, 2021 MCQ Q52, 2022 MCQ Q55).
High Yield – DDx from Lecture Slide
The differential diagnosis of a patient with fever and confusion includes: [1]
- CNS infections
- Other non-CNS infections (+/- systemic involvement) with encephalopathy (septic, metabolic, toxic)
- Sepsis in patients with primary psychiatric disorder
- Autoimmune encephalitis (e.g. anti-NMDA receptor encephalitis)
- Inflammatory disorders affecting the brain (e.g. vasculitis, cerebral lupus)
- Sepsis with nonconvulsive status epilepticus
- Thyroid storm
Why This Matters
Not every febrile confused patient has meningitis. The lecturer deliberately lists these to remind you to think broadly first, then narrow. A patient with a UTI and delirium is "non-CNS infection with encephalopathy." A patient on lithium with fever and confusion might have thyroid storm or drug toxicity. Always ask: Is the brain the primary problem, or is the brain secondarily affected by a systemic process?
Encephalopathy = a disorder of the brain resulting in an altered mental state (impaired cognition, orientation and consciousness) [1]
This definition is important: encephalopathy is a clinical description, not a specific diagnosis. It can be caused by infection, metabolic derangement, toxins, organ failure, etc.
Part 2: Clinical Approach — History
| Element | Why It Matters |
|---|---|
| Age | Organism spectrum changes with age (see bacterial meningitis organisms below) |
| Fever — onset, duration, pattern | Acute (bacterial) vs subacute/chronic (TB, fungal) |
| Headache — onset, duration, nature, location, severity | Severe generalised headache typical of meningitis |
| Features of meningism — neck stiffness, photophobia | Hallmark of meningeal inflammation |
| Features of raised ICP — vomiting | Suggests complications (cerebral oedema, hydrocephalus) |
| Consciousness and mental state | Distinguishes meningitis (cerebral function preserved) from encephalitis (cerebral function abnormal) |
| Other neurological symptoms | Focal signs suggest encephalitis or abscess |
| Features of underlying infections (respiratory, ENT, dental, GI, urinary) | Identifies the primary focus / route of spread |
| Progression of symptoms | Rapid = bacterial; Insidious = TB/fungal |
| Previous treatment — esp. recent antibiotics | Partially treated bacterial meningitis can mimic TB/viral CSF pattern |
| Travel / contact history | Japanese encephalitis (Asia), meningococcal outbreaks, TB contacts |
| Element | Why It Matters |
|---|---|
| History of tuberculosis | TB meningitis is very common in Hong Kong |
| Immunocompromised state (DM, immunosuppressants, HIV) | Expanded organism list: Listeria, Cryptococcus, Toxoplasma, CMV |
| Immunisation history | H. influenzae type B, meningococcal vaccines |
| Occupational history | Streptococcus suis meningitis — those who work with pigs/pork industry (meat processors, butchers) [1] — a Hong Kong–relevant pathogen |
| Drug history — immunosuppressants, recent antibiotics | Steroids, azathioprine, cyclosporine all increase infection risk |
| Other drug use including OTC and illicit | Ecstasy can cause SIADH and hyponatraemic encephalopathy; IV drug use → endocarditis → septic emboli → brain abscess |
Exam Trap
Streptococcus suis meningitis is a favourite HKUMed exam question because it's locally relevant. Always ask about occupational exposure to pigs. Complication: sensorineural hearing loss [2].
Physical examination should include:
- Conscious level (GCS) and orientation
- Vital signs and temperature
- Signs of meningeal irritation — neck stiffness, Kernig's sign, Brudzinski's sign
- Focal neurological signs
- Skin rash (morbilliform, petechial, purpuric in meningococcal meningitis; vesicular in HSV/VZV)
- Other systems — dental, ENT (otitis media, sinusitis), respiratory, abdominal, cardiovascular (infective endocarditis)
- Fundi for papilloedema
Signs of Meningeal Irritation — Explained [1]
| Sign | How to Elicit | Positive When | Why It Works |
|---|---|---|---|
| Nuchal rigidity / neck stiffness | Passive flexion of the neck | Resistance to flexion | Inflamed meninges stretch when neck flexes, causing pain and reflex muscle spasm |
| Kernig's sign | Patient supine, hip and knee flexed to 90°, then passively extend the knee | Passive extension of knee is limited by pain | Extending the knee stretches the sciatic nerve roots traversing inflamed meninges |
| Brudzinski's sign | Flex the patient's neck passively | Involuntary flexing of the hips and knees | Neck flexion stretches the spinal meninges; the body reflexively flexes the legs to reduce meningeal tension |
Clinical Pearl
Meningeal signs can be absent in the very young, the elderly, the immunosuppressed, and the deeply comatose. A negative Kernig's/Brudzinski's does NOT exclude meningitis.
Part 4: Investigations
| Test | Rationale |
|---|---|
| CBC + differential | Leucocytosis (bacterial), lymphopenia (viral/TB), thrombocytopenia (DIC in meningococcal sepsis) |
| Basic biochemistry (LFT, RFT) | Baseline organ function; hyponatraemia from SIADH is a recognised complication |
| Inflammatory markers (ESR, CRP) | CRP typically very high in bacterial, may be lower in viral |
| Blood culture | Essential before antibiotics; identifies organism in ~50% of bacterial meningitis |
| Clotting profile | Rule out DIC; also needed before LP (INR > 1.4 or plt < 50 → contraindication to LP) |
| Blood gas | Metabolic acidosis in sepsis; respiratory failure in severe encephalitis |
CT brain (non-contrast):
- To exclude mass lesion (e.g. brain abscess, malignancy) before lumbar puncture (risk of coning) especially if patient has impaired consciousness or focal neurological signs
- Should not delay treatment of presumed CNS infections
- May reveal hypodensities (e.g. in encephalitis, ischaemic stroke complicating meningitis)
Why CT before LP? The Monro-Kellie doctrine explains that if there is already a mass or significant oedema shifting brain contents, removing CSF from below via LP creates a pressure gradient that can cause transtentorial (uncal) herniation — a rapidly fatal event. CT identifies these contraindications.
Critical point: If clinical suspicion for meningitis is high and CT is needed, give empirical antibiotics BEFORE sending the patient to CT. Never let imaging delay treatment.
| Modality | When / Why |
|---|---|
| CT brain with contrast | Brain abscess (ring enhancement), meningeal enhancement, tuberculomas |
| MRI brain with contrast | Superior to CT for meningeal enhancement, encephalitic changes, tuberculomas |
| EEG | Generalised slow waves (encephalopathy); periodic lateralising epileptiform discharges (PLEDs) in HSV encephalitis; nonconvulsive status epilepticus |
| Echocardiogram | If suspecting infective endocarditis as the source |
| Imaging of sinuses | If suspecting direct spread from sinusitis |
Part 5: Lumbar Puncture — The Key Investigation
- ~500 mL/day produced (by choroid plexus)
- Absorbed across the arachnoid villi by a valve-like mechanism
- Functions: mechanical support, regulating ionic composition, removal of metabolites
- Total volume in adults: ~150 mL; turnover ~3–4 times per day
Diagnostic:
- CNS infections
- SAH where CT non-contrast is non-revealing (xanthochromia)
- Inflammatory conditions of the CNS (e.g. CNS vasculitis)
- Demyelinating disorders (e.g. multiple sclerosis — oligoclonal bands)
- Malignant disorders of the CNS (cytology)
Therapeutic:
- Analgesia (e.g. epidural anaesthesia)
- Intrathecal chemotherapy
- CSF removal (e.g. communicating hydrocephalus)
| Contraindication | Why |
|---|---|
| Intracranial lesion causing mass effect or significant cerebral oedema | LP may result in cerebral herniation |
| Severe coagulopathy (INR > 1.4) or thrombocytopenia (platelet < 50 × 10⁹/L) | Spinal haematomas causing spinal cord compromise |
| Local congenital lesions | Structural abnormality at LP site |
| Local suppuration | Risk of introducing infection into the subarachnoid space |
Past Paper Alert – LP Contraindication
2020 MCQ Q34: Patient with papilloedema and plt 100 × 10⁹/L — the answer is A (Increased ICP) because papilloedema = raised ICP = mass effect suspected despite normal CT. However, note that the platelet count of 100 is above the threshold of 50 and PT is normal, so coagulopathy is NOT the contraindication. This tests whether you know the platelet threshold ( < 50) and the INR threshold ( > 1.4) [3].
Headache, radicular symptoms and low back pain, bleeding, infection, cerebral herniation
Minimum 5 mL should be collected
- Opening pressure (normal: 6–20 cm H₂O, fluctuates with respiration)
- Colour (normal: colourless; turbid/pus/xanthochromia/blood-stained)
- Total cell count + differential (normal: < 5 cells/mL)
- Glucose (+ paired serum glucose) ← this is mandatory; CSF glucose must always be interpreted as a ratio
- Protein (normal: 0.15–0.45 g/L)
Xanthochromia — indicates presence of red cells in CSF. With time, red cells break down, releasing haeme, which is subsequently degraded into the yellow-green pigment bilirubin causing the characteristic yellow colour [1]
| Test | Target |
|---|---|
| Gram smear, bacterial culture | Pyogenic bacteria |
| Viral titre, culture, and PCR for HSV, enteroviruses, VZV | Viral aetiologies |
| CSF + serum Japanese B virus–specific IgM | If clinical suspicion |
| Ziehl-Neelsen smear, mycobacterial culture, PCR for M. tuberculosis | TB (low sensitivity: ZN < 15%, culture < 50%, PCR ~50–90%) |
| Indian ink exam for Cryptococcus, fungal culture, +/- cryptococcal Ag | Fungal meningitis |
| Multiplex PCR | Broad panel covering common bacterial, viral, and fungal organisms |
Non-microbiological tests:
- Oligoclonal bands — demyelinating disorders
- Cytology — CNS malignancy
- Autoimmune markers — autoimmune encephalitis (e.g. anti-NMDA receptor antibodies)
Part 6: CSF Interpretation — THE High-Yield Table
Exam Cornerstone — CSF Patterns
This table appears in almost every written paper. You MUST be able to classify a CSF result into the correct category.
| Parameter | Normal | Viral | Bacterial | Tuberculous | Fungal |
|---|---|---|---|---|---|
| Opening pressure | 6–20 cmH₂O | Normal/High | ↑ | ↑ | ↑ |
| Cells/mm³ | < 5 | 50–1,000 | 1,000–5,000 | 50–300 | 20–500 |
| Predominant cell type | Mononuclear | Mononuclear | Polymorphonuclear | Mononuclear | Mononuclear |
| CSF/plasma glucose ratio | *** > 50%*** | Normal | ↓ ( < 50%) | ↓ | ↓ |
| Protein (g/L) | *** < 0.45*** | Normal/mild ↑ | ↑ | ↑ | ↑ |
N.B. Partially-treated bacterial meningitis and malignant meningitis (e.g. due to lymphoma, leukaemia or carcinomatosis) may also have a CSF picture with lymphocytic predominant pleocytosis with low glucose and raised protein [1]
-
Look at the glucose ratio first (CSF glucose ÷ serum glucose):
- Normal ratio → likely viral
- Low ratio ( < 50%) → bacterial, TB, fungal, partially-treated bacterial, or malignant
-
Look at the predominant cell type:
- PMN predominant + low glucose → bacterial meningitis
- Lymphocyte predominant + low glucose → TB, fungal, partially-treated bacterial, malignant
- Lymphocyte predominant + normal glucose → viral
-
Look at protein and cell count magnitude:
- Very high cells (1,000–5,000) with PMN → strongly bacterial
- Moderate cells (50–300) with lymphocytes → TB
2021 MCQ Q52 [4]: CSF: 80 cells/µL, 75% lymphocytes, protein 1.0 g/L, glucose 3.6 mmol/L, serum glucose 6 mmol/L.
- Glucose ratio = 3.6/6 = 60% (normal!)
- Lymphocytic predominance
- Protein raised
- This looks like a viral pattern — EXCEPT the protein is quite high (1.0 g/L). However, glucose ratio is normal, ruling out bacterial and TB.
- But wait — could this be early TB? In typical viral meningitis, protein is only mildly elevated. With protein of 1.0 and modestly elevated cells, the best fit given normal glucose ratio is viral meningitis (Answer D).
Actually — re-read: Glucose ratio = 60% which is > 50%. The cell count is moderate with lymphocytic predominance. Protein is elevated but glucose is normal. The answer choices are bacterial, abscess, TB, or viral. Answer: D — Viral meningitis. But this is a tricky one because the protein is higher than expected for typical viral — the exam is testing whether you fixate on protein alone or use the glucose ratio correctly.
2022 MCQ Q55 [5]: CSF: 180 cells/µL, 70% neutrophils/25% lymphocytes, protein 2.5 g/L, glucose 5.2 mmol/L, serum glucose 14 mmol/L.
- Glucose ratio = 5.2/14 = 37% ( < 50% → low!)
- PMN predominant
- High protein
- This is classic bacterial meningitis (Answer A).
Exam Trap — Glucose Ratio Calculation
The 2022 question is designed to trick you: the CSF glucose of 5.2 mmol/L looks normal in absolute terms. But the serum glucose is 14 mmol/L (the patient likely has diabetes). The RATIO is 37% — clearly low. This is why the lecture emphasises always get a paired serum glucose [1]. Without the serum value, you'd miss bacterial meningitis.
Part 7: Meningitis
Inflammation of the leptomeninges: caused by infection (bacterial, viral, fungal), neoplastic infiltration, or drug-induced aseptic meningitis
| Type | Timeframe | Typical Organisms |
|---|---|---|
| Acute meningitis | Hours to days | Bacteria or viruses |
| Subacute/chronic meningitis | Days to weeks to > 4 weeks | Mycobacteria, fungi, or atypical bacteria |
Routes of infection:
- Direct spread from nearby structures — respiratory tract, ear (otitis media), sinus (sinusitis), dental infections, skull fractures
- Haematogenous spread from a distant septic focus — e.g. pneumonia, infective endocarditis
Bacterial Meningitis
Infection stimulates immune response → pia-arachnoid membrane infiltrated with inflammatory cells → pus forms which can organise to form adhesions →
- Obstruct free flow of CSF → hydrocephalus
- Damage cranial nerves at base of brain → hearing loss
- Obliterative endarteritis of leptomeningeal arteries passing through meningeal exudate → secondary cerebral infarction
This is a beautiful pathophysiology chain. Understand why each complication happens:
- Hydrocephalus: pus and adhesions block CSF pathways, especially at the base of the brain → communicating hydrocephalus (or non-communicating if foramina blocked)
- Cranial nerve palsies: nerves traverse the subarachnoid space at the skull base through pools of inflammatory exudate
- Cerebral infarction: inflammation of small arteries running through infected meninges → vessel wall damage → thrombosis → stroke in a young person with meningitis
| Clinical Scenario | Organisms |
|---|---|
| 18–50 years | Streptococcus pneumoniae, Neisseria meningitidis |
| *** > 50 years*** | + Gram-negative bacilli (Klebsiella, E. coli, Salmonella) |
| Immunocompromised | + Listeria monocytogenes, Pseudomonas aeruginosa |
| Occupational/pig exposure | Streptococcus suis |
| Contaminated fresh water | Naegleria fowleri & other free-living amoeba |
| Head trauma/post-neurosurgery/intrathecal injection | Staphylococcus aureus, Staph. epidermidis, aerobic Gram-negative bacilli |
High Yield - Ampicillin for Listeria
From GC 106 / Microbiology: Consider adding ampicillin for Listeria coverage on top of ceftriaxone if you encounter high-risk patients with meningitis (elderly, immunocompromised, neonates) [6]. This is because 3rd-generation cephalosporins do NOT cover Listeria — a classic exam discriminator.
- Headache, fever, meningeal irritation (neck stiffness, Kernig's, Brudzinski's)
- Severe meningitis: impaired consciousness (encephalopathy, cerebral oedema), focal neurological signs
Meningococcal sepsis — complications:
- Meningitis
- Rash (morbilliform, petechial, purpuric)
- Septic shock
- Disseminated intravascular coagulation
- Renal failure
- Peripheral gangrene
The petechial/purpuric rash of meningococcal disease is due to DIC and small-vessel thrombosis. It is non-blanching — press a glass on it and it doesn't disappear. This is a medical emergency.
- High mortality rate of 80% if untreated
- Empirical high-dose antibiotics that penetrate the blood-brain barrier, subsequently guided by culture results
- Benefit of adjunctive dexamethasone remains inconclusive (but widely used in practice for pneumococcal meningitis to reduce inflammatory damage — the GC lecture framing says "inconclusive")
- Close contacts of patients with Haemophilus influenzae type B and Neisseria meningitidis require chemoprophylaxis (e.g. rifampicin or ciprofloxacin)
Very common cause of meningitis in Hong Kong
This is emphasised because Hong Kong has a high TB burden compared to most developed cities.
Pathophysiology:
Rupture of a superficial infective granuloma on the pia mater into the subarachnoid space. May have concomitant pulmonary/systemic disease.
Clinical presentation:
Onset slower than bacterial meningitis. Fever and headache for several days to weeks.
From senior notes [7]: TB meningitis classically presents in three phases:
- Prodromal phase (1–3 weeks): malaise, headache, low-grade fever, personality changes
- Meningitic phase: meningism, protracted headache, vomiting, lethargy, confusion, cranial nerve/long tract signs
- Paralytic phase: stupor, seizure, hemiparesis, death if untreated
Investigations [1]:
- LP: Low sensitivity — ZN smear < 15%, CSF culture < 50%, TB PCR ~50–90%
- Neuroimaging (CT/MRI): hydrocephalus, meningeal enhancement, intracranial tuberculomas, cerebral infarct
- CXR, sputum AFB smear and culture
Management [1]:
- High mortality and morbidity amongst survivors
- Anti-TB treatment should be started if suspicious of TB meningitis (even if smear and PCR negative as limited sensitivity)
- Isoniazid, rifampicin, pyrazinamide, ethambutol
- Duration: at least 9–12 months, often extended to 18 months if immunocompromised (e.g. HIV) due to higher risk of relapse and developing drug-resistant TB
- Concomitant use of dexamethasone (tapering dose, given parenterally initially) — reduces risk of death and disability
Dexamethasone in TB Meningitis vs Bacterial Meningitis
In TB meningitis, adjunctive dexamethasone has strong evidence for reducing mortality and disability (the lecture states this clearly). In contrast, for bacterial meningitis, the lecture says benefit is inconclusive. This is a potential exam discriminator.
Presentation:
- Subacute onset of headache and cognitive impairment
- 50% have underlying immunodeficiency (HIV, immunosuppressants, transplant recipients)
Investigations:
- LP: lymphocytic pleocytosis, high protein, low CSF-to-serum glucose
- Positive Indian ink exam (50%) — the capsule of Cryptococcus neoformans creates a "halo" (negative staining) around the budding yeast
- Positive CSF cryptococcal antigen (85%), fungal culture (90%)
- Serum cryptococcal antigen
Management:
- IV amphotericin B + oral flucytosine (induction) → prolonged oral fluconazole (maintenance)
- Total duration usually weeks to months
Why this regimen? Amphotericin B is fungicidal and the most potent antifungal but is nephrotoxic. Flucytosine has synergistic activity. Fluconazole is well tolerated for long-term maintenance to prevent relapse.
- Benign and self-limiting illness
- Much less serious than bacterial meningitis unless there is associated encephalitis
Common viruses:
Enteroviruses (echo, Coxsackie, polioviruses), HSV types 1 and 2, VZV, CMV, EBV, HIV
Management:
Symptomatic treatment. Usually self-limiting with complete recovery within days without specific therapy.
- Meningeal adhesions → raised ICP, obstructive hydrocephalus, cranial nerve palsies
- Arteritis / thrombophlebitis → cerebral infarction
- Seizures and epilepsy
- Local spread of infection (cerebritis, cerebral abscess, subdural effusion/empyema)
- Intellectual impairment, cerebral palsy
- SIADH
- DIC
- Septic shock
Part 8: Encephalitis
Inflammation of the brain parenchyma, mostly viral. Usually with meningitis (meningoencephalitis).
Key distinguishing feature from meningitis [8]: In meningitis, cerebral function is preserved (patient may be drowsy but cognitively intact). In encephalitis, there is abnormal cerebral function — altered mental status, personality/behavioural changes, sensory/motor deficits, speech and movement disorders.
Herpes viruses (HSV, VZV) — HSV-1 most common cause Enteroviruses, Influenza virus, Adenovirus, CMV, EBV, HIV Flaviviruses (e.g. Japanese encephalitis virus) Rabies virus
Inflammatory response involving the cortex, white matter, basal ganglia and brainstem Distribution of lesions varies with virus type:
| Virus | Predilection Site |
|---|---|
| Herpes simplex | Frontal and temporal lobes |
| CMV | Areas adjacent to the ventricles (ventriculitis) |
| Japanese encephalitis virus | Thalamus |
Inclusion bodies may be present in neurons and glial cells with infiltration of polymorphonuclear cells in the perivascular space Neuronal degeneration and diffuse glial proliferation, often with cerebral oedema
- Fever
- Headache
- Focal neurological signs — dysphasia, hemiplegia, visual field defects
- Seizures
- Confusion
- Altered level of consciousness — mild lethargy to deep coma
From the Neurology Introduction lecture [9]: the triad of viral encephalitis is fever, confusion and convulsion.
Neuroimaging:
- CT: hypodensity in frontotemporal lobes (HSV)
- MRI: hyperintensity (T2/FLAIR) in frontotemporal lobes (HSV); bilateral thalamic hyperintensity (Japanese encephalitis)
CSF:
- Lymphocytic predominant pleocytosis (neutrophils may predominate in early stages)
- Normal glucose, mild elevation in protein
- Abnormal viral culture / PCR
EEG:
Periodic slow-wave activity / lateralising epileptiform discharges (PLEDs) involving frontotemporal lobes in HSV encephalitis
Aciclovir 10 mg/kg IV three times per day for 2–3 weeks for HSV encephalitis Should be started in ALL patients with suspected viral encephalitis Significantly reduced mortality of HSV encephalitis Antiseizure medications may be needed
High Yield — Aciclovir for ALL Suspected Viral Encephalitis
Do NOT wait for PCR results to start aciclovir. HSV encephalitis has 50–70% mortality if untreated [10] but is treatable. The risk of giving aciclovir empirically is minimal compared to the catastrophe of missing HSV encephalitis.
Part 9: Brain Abscess (Suppurative Brain Infection)
Bacteria may enter the brain substance by:
- Penetrating trauma
- Direct spread from paranasal sinuses or the middle ear
- Haematogenous spread — may lead to multiple abscesses
- Untreated congenital heart disease is a risk factor (right-to-left shunting can result in bacteria directly affecting the brain; increased risk of developing infective endocarditis; immunocompromised state)
Why right-to-left shunts? Normally, blood passes through the lungs where the pulmonary capillary bed filters out bacteria. With an R→L shunt (e.g. Fallot's tetralogy), bacteria bypass the lung filter and seed the brain directly.
Initial infection leads to local suppuration followed by loculation of pus within a surrounding wall of gliosis
This explains the ring enhancement on contrast CT — the capsule of gliosis enhances with contrast, while the centre (pus) does not.
Can present over days to weeks
- Headache
- Changes in mental status
- Focal neurological deficits
- Seizures
- Raised intracranial pressure
Note: fever may be absent or low-grade in brain abscess — unlike meningitis where fever is typically high.
| Source of Infection | Organisms |
|---|---|
| Otitis media, mastoiditis | Streptococci, Bacteroides spp. |
| Sinusitis | Streptococci, Bacteroides, Staph. aureus, Haemophilus spp. |
| Dental infection | Mixed anaerobes with Fusobacterium, Bacteroides spp., streptococci |
| Penetrating trauma / post-surgery | Staph. aureus, streptococci |
| Infective endocarditis | Staph. aureus, streptococci |
| HIV | Toxoplasma gondii, Nocardia spp., Cryptococcus neoformans |
- CT brain: single or multiple hypodense lesions, ring enhancement with contrast, surrounding cerebral oedema
- Lumbar puncture potentially hazardous (mass effect → herniation risk)
- Stereotactic CT-guided aspiration or incision and drainage are important to aid microbiological diagnosis
LP Contraindicated in Brain Abscess
A brain abscess is a mass lesion. LP is dangerous because it can cause herniation. Diagnosis relies on imaging + surgical aspiration for microbiology, NOT LP.
- Broad spectrum antimicrobial therapy covering both aerobic and anaerobic bacteria
- E.g. Ceftriaxone IV + Metronidazole IV
- Likely source of infection can help guide antibiotic choice
- Neurosurgical patients — consider adding IV vancomycin
- Surgical drainage by burr-hole aspiration may be necessary
- Anti-seizure medications if seizures develop
- IV mannitol / steroids if significant cerebral oedema
- 10–20% mortality
Why ceftriaxone + metronidazole? Ceftriaxone covers aerobic Gram-positives and Gram-negatives; metronidazole covers anaerobes (Bacteroides, Fusobacterium) which are common in brain abscesses from dental/ENT/otogenic sources [6].
Autoimmune encephalitis is a differential diagnosis of patients presenting with fever and confusion
- Rare
- May be associated with underlying malignancies and infections that have triggered an immune response against the brain parenchyma
- Most common: anti-NMDA (N-methyl-D-aspartate) receptor encephalitis
Demographics and associations:
- Most commonly affects young women and children
- Associated with ovarian teratomas
Clinical presentation:
- Viral-like prodrome
- Neuropsychiatric symptoms (altered cognition, behavioural changes — psychosis, aggression, catatonia)
- Abnormal movements (orofacial, limb or trunk dyskinesias)
- Seizures
- Altered consciousness
- Autonomic dysfunction
Investigations and Management:
- Initial investigation approach similar to CNS infections
- Infective aetiologies must be excluded first
- Blood and CSF for autoimmune antibodies (e.g. anti-NMDA receptor antibodies)
Management:
- Close monitoring (refractory seizures, autonomic instability)
- Immunotherapy:
- Acute: high-dose IV prednisolone, IVIG, plasmapheresis
- Subsequent: oral corticosteroids / steroid-sparing agents
- Anti-seizure medications
- Supportive care
- Search for and remove underlying tumour (e.g. ovarian teratoma)
Anti-NMDA Receptor Encephalitis — Exam Favourite
Young woman + psychiatric symptoms + seizures + abnormal movements + autonomic instability → think anti-NMDA receptor encephalitis. Always look for an ovarian teratoma on imaging. This condition bridges neurology, psychiatry, and immunology.
Part 11: General Principles of CNS Infections [1]
| Structure | Disease |
|---|---|
| Meninges | Meningitis |
| Brain parenchyma | Encephalitis |
| Spinal cord | Myelitis |
| Pus within brain parenchyma | Brain abscess |
| Pus outside brain parenchyma | Epidural or subdural empyema |
Bacteria, viruses, fungi, protozoa (rare)
Acute (hours–days), subacute (days–weeks), chronic (symptoms > 4 weeks)
- Common condition with high mortality and morbidity if treatment delayed
- Quick septic workup including blood culture BEFORE start of antibiotics
- Early lumbar puncture if no contraindications
- Initial high-dose broad-spectrum parenteral antibiotics that penetrate the blood-brain barrier, subsequent streamlining with availability of microbiological results
- Regular monitoring of neurological status and vital signs
- Look for the primary infective focus AND complications
- Close liaison with microbiologist, neurologist and neurosurgeon
| Suspected Condition | Empirical Treatment |
|---|---|
| Bacterial meningitis | High dose IV ceftriaxone (or meropenem) |
| HSV/VZV coverage | IV aciclovir |
| MRSA suspected | Add IV vancomycin |
| TB meningitis | IRPE (isoniazid, rifampicin, pyrazinamide, ethambutol) + dexamethasone |
| Cryptococcal meningitis | IV amphotericin B + flucytosine → oral fluconazole |
| Brain abscess | IV ceftriaxone + IV metronidazole (+/- vancomycin if post-neurosurgery) |
| Investigation | When |
|---|---|
| CXR | All patients (TB screening, pneumonia source) |
| NPA for respiratory viruses | If respiratory symptoms |
| Sputum for Gram smear/culture, AFB | If TB suspected |
| Blister fluid for viral studies | Vesicular rash (HSV, VZV) |
| Urine microscopy and culture | Exclude UTI as source |
| Blood for TFTs | Exclude thyroid storm |
| Urine for toxicology | Drug-induced encephalopathy |
Exam Intelligence
SAQ (see 2019 Q10 [3]):
- "A 35-year-old man with fever and confusion for 2 days, develops generalised tonic-clonic convulsion. No focal neurological deficit."
- Most likely clinical diagnosis? → Viral encephalitis / meningoencephalitis
- Three investigations? → CT brain, LP with CSF analysis, blood culture (+/- MRI, EEG)
- Three infective causes? → HSV, enterovirus, Japanese encephalitis
- Empirical antimicrobial therapy? → IV aciclovir + IV ceftriaxone (cover both viral and bacterial until differentiated)
MCQ — CSF interpretation (appears almost every year):
- Given CSF values + serum glucose → calculate ratio → classify
- Key discriminator: glucose ratio > 50% = viral; < 50% + PMN = bacterial; < 50% + lymphocyte = TB/fungal/partially-treated bacterial
MCQ — LP contraindications:
- Know platelet threshold ( < 50) and INR threshold ( > 1.4)
- Papilloedema = raised ICP = contraindication even if CT normal
MCQ — Organism associations:
- S. suis + pigs
- Cryptococcus + immunosuppression
- HSV encephalitis + temporal lobe involvement
- Japanese encephalitis + thalamus
- Young woman + psychiatric symptoms + dyskinesia = anti-NMDA receptor encephalitis
| Trap | How to Avoid |
|---|---|
| Interpreting CSF glucose in absolute terms without serum glucose | Always calculate the ratio |
| Assuming normal CT excludes raised ICP | Papilloedema on fundoscopy is a clinical sign of raised ICP regardless of CT |
| Waiting for cultures before starting treatment | Treat empirically first, streamline later |
| Assuming viral meningitis CSF = viral encephalitis CSF | They're similar (lymphocytic, normal glucose), but encephalitis has abnormal brain function clinically |
| Confusing meningitis complications with encephalitis features | Meningitis can cause seizures (from metabolic derangement or focal ischaemia), but the hallmark of encephalitis is diffuse cerebral dysfunction |
| Partially-treated bacterial meningitis mimicking TB | History of recent antibiotic use is crucial |
Q1 (SAQ style): A 45-year-old butcher presents with fever, headache, neck stiffness, and hearing loss. CSF shows PMN pleocytosis with low glucose. What is the most likely organism? (Streptococcus suis)
Q2 (MCQ style): CSF: cells 200/µL (80% lymphocytes), protein 1.2 g/L, glucose 1.5 mmol/L, serum glucose 5 mmol/L. Most likely diagnosis? (TB meningitis — lymphocytic, low ratio [30%], high protein)
Q3: List 3 contraindications to lumbar puncture. (Mass lesion with mass effect, severe coagulopathy [INR > 1.4 or plt < 50], local infection at LP site)
Q4: Name the empirical antimicrobial regimen for suspected bacterial meningitis with concurrent HSV coverage. (IV ceftriaxone + IV aciclovir)
Q5: Which virus causes encephalitis with predilection for the temporal and frontal lobes? (HSV-1)
Q6: What adjunctive therapy is proven to reduce mortality in TB meningitis? (Dexamethasone)
High Yield Summary
Fever + confusion = CNS infection until proven otherwise.
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Systematic approach: History (age, onset, travel, occupation, immunosuppression) → Examination (GCS, meningeal signs, focal neuro, rash, fundi) → Investigations (bloods + CT brain if focal signs/impaired consciousness → LP → CSF analysis)
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CSF interpretation is the single highest-yield exam topic: Calculate glucose ratio (need paired serum glucose). PMN + low glucose = bacterial. Lymphocyte + normal glucose = viral. Lymphocyte + low glucose = TB/fungal/partially-treated bacterial/malignant.
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Empirical treatment: IV ceftriaxone + IV aciclovir. Do NOT delay for investigations. Add ampicillin if Listeria risk; add vancomycin if MRSA risk; add metronidazole for brain abscess.
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TB meningitis: Very common in HK. Start IRPE + dexamethasone even if smear/PCR negative. Duration ≥ 9–12 months.
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HSV encephalitis: Most common cause of viral encephalitis. Temporal/frontal predilection on MRI. Aciclovir 10 mg/kg TDS for 2–3 weeks. Start empirically.
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Brain abscess: Ring-enhancing lesion on contrast CT. LP contraindicated. Ceftriaxone + metronidazole. Surgical drainage often needed.
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Anti-NMDA receptor encephalitis: Young women, ovarian teratoma, psychiatric symptoms + dyskinesia + seizures + autonomic dysfunction. Treat with immunotherapy after excluding infection.
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Chemoprophylaxis for close contacts of H. influenzae type B and N. meningitidis (rifampicin or ciprofloxacin).
Active Recall - Fever and Confusion: Meningitis, Encephalitis, Brain Abscess
[1] Lecture slides: GC 051. Fever and confusion_meningitis and encephalitis; suppurative brain infection.pdf (all pages) [2] Senior notes: Maksim Medicine Notes.pdf (p.196 — CNS infections, S. suis and SNHL) [3] Past papers: 2019 Fourth Summative SAQ.pdf (Q10 — fever and confusion with convulsion) [4] Past papers: 2021 Fourth Summative Assessment MCQ.pdf (Q52 — CSF interpretation) [5] Past papers: 2022 Fourth Summative MCQ.pdf (Q55 — CSF interpretation with high serum glucose) [6] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf (p.27 — ampicillin for Listeria, metronidazole for anaerobes) [7] Senior notes: Ryan Ho Respiratory.pdf (p.79 — TB meningitis triphasic illness) [8] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1179 — meningitis vs encephalitis distinction) [9] Lecture slides: Neurology- Introduction to CNS investigations and neurological emergencies.pdf (p.110 — viral encephalitis triad) [10] Senior notes: Ryan Ho Neurology.pdf (p.148 — HSV encephalitis 50–70% mortality if untreated)
High White Cell Count
Leukocytosis is an elevation of the total white blood cell count above the normal range (typically >11,000/μL), indicating infection, inflammation, stress, or hematologic malignancy.
Fever After A Blood Transfusion
A febrile reaction occurring during or shortly after a blood transfusion, most commonly caused by recipient antibodies against donor leukocyte antigens or cytokines accumulated in stored blood products.