Meningitis and Encephalitis — Written Clinical Reasoning

SAQ 1 — Empiric and Targeted Management of Bacterial Meningitis in an Immunocompromised Patient (20 marks, 30 minutes)

Prompt: Outline your integrated management plan for this patient, including the immediate empiric therapy with exact drugs, doses, and rationale; the choice of adjunctive therapy; the interpretation of his CSF findings; the anticipated organism and how you will confirm it; the management of his comorbidities; and the complications you must monitor for. Justify each decision with reference to evidence. [1]

Model Answer

Immediate empiric therapy (5 marks): [1]

The priority is to start empiric antibiotics immediately — this patient has a high clinical probability of acute bacterial meningitis and any delay increases mortality [2]. The empiric regimen must account for his specific risk factors:

• Ceftriaxone 2 g IV every 12 hours — covers S. pneumoniae and N. meningitidis
• Vancomycin (loading dose 25 to 30 mg/kg, then 15 to 20 mg/kg every 12 hours, targeting trough 15 to 20 mg/L) — covers penicillin-resistant pneumococcus
• Ampicillin 2 g IV every 4 hours — essential for Listeria monocytogenes cover. This patient is over 50, immunocompromised (rituximab, CLL), and has alcohol use disorder — all are independent risk factors for Listeria. Listeria is intrinsically resistant to all cephalosporins; ceftriaxone alone will not treat it
• Aciclovir 10 mg/kg IV every 8 hours — his reduced GCS and fever could represent encephalitis rather than (or in addition to) meningitis; empiric aciclovir is appropriate until HSV PCR is negative
• Dexamethasone 10 mg IV immediately — given before or with the first antibiotic dose, per the de Gans and van de Beek trial [1] and the 2015 Cochrane review [3]. If the Gram stain or culture confirms pneumococcus, continue for 4 days (10 mg IV every 6 hours); stop if meningococcal or another organism

The clinical reasoning is that immunocompromise and alcohol use disorder broaden the empiric cover to include Listeria, and the encephalopathic presentation warrants empiric aciclovir. The dexamethasone is given before antibiotics to suppress the inflammatory burst caused by antibiotic-induced bacterial lysis. [1]

CSF interpretation and likely organism (4 marks): [1]

The CSF pattern is classic for acute bacterial meningitis:

• Neutrophilic pleocytosis (1800 cells, 75 per cent neutrophils) — bacterial pattern
• Very low glucose (0.8 mmol/L; CSF:serum ratio 0.1, well below 0.4 threshold) — bacterial, TB, or fungal
• High protein (3.5 g/L) — consistent with bacterial or TB
• Raised opening pressure (30 cm of water) — consistent with bacterial meningitis [1]

In a 72-year-old immunocompromised patient with alcohol use disorder, the differential organisms are:

1. Streptococcus pneumoniae — the most common cause in adults regardless of immune status
2. Listeria monocytogenes — given his age, immunocompromise, and alcohol use
3. Gram-negative bacilli (including Pseudomonas if neutropenic) [1]

The CSF Gram stain (pending) and culture will identify the organism. The meningitis/encephalitis multiplex PCR panel on CSF (which detects S. pneumoniae, N. meningitidis, H. influenzae, L. monocytogenes, and C. neoformans DNA) is useful because it can provide a result within hours and is not affected by prior antibiotics. [1]

Adjunctive therapy and its timing (3 marks): [1]

Dexamethasone 10 mg IV before or with the first antibiotic dose is the critical adjunctive therapy. The de Gans trial showed benefit in pneumococcal meningitis (unfavourable outcomes reduced from 52 to 26 per cent) [1]. The Cochrane review confirmed benefit in high-income countries, especially for hearing loss and neurological sequelae [3]. The key is timing: the steroid must be given before the first antibiotic dose, because the benefit accrues by suppressing the inflammatory cascade triggered by bacterial lysis. Giving it after antibiotics provides little benefit. Continue for 4 days (every 6 hours) if pneumococcal; stop if the organism is Listeria or meningococcal (no evidence of benefit and potential harm from immunosuppression in Listeria, which is intracellular).

Management of comorbidities (4 marks): [1]

• Chronic lymphocytic leukaemia and rituximab: This patient is functionally immunocompromised with impaired humoral immunity. He is at risk of encapsulated organisms (pneumococcus), Listeria, and opportunistic pathogens. After recovery, discuss vaccination (pneumococcal, meningococcal, Hib) and consider the timing of future rituximab. Consult haematology and infectious diseases.
• Diabetes: Monitor glucose closely; stress hyperglycaemia worsens neurological outcome. Use an insulin sliding scale; target glucose 6 to 10 mmol/L.
• Alcohol use disorder: Risk of withdrawal (CIWA monitoring, benzodiazepine protocol). Check thiamine and give parenteral thiamine before any glucose. Assess for alcoholic ketoacidosis and deranged LFTs.
• Hypotension (BP 95/60): He is in septic shock. Aggressive fluid resuscitation with crystalloid, early vasopressor support (noradrenaline) if fluid-refractory, and admit to ICU. Serial lactate to guide resuscitation. [1]

Complications to monitor (4 marks): [1]

1. SIADH and hyponatraemia: Common in bacterial meningitis. Check sodium daily. Avoid hypo-osmolar fluids. Treat sodium under 125 with hypertonic saline or fluid restriction; correct no faster than 8 mmol/L in 24 hours to avoid osmotic demyelination.
2. Seizures: Occur in 15 to 30 per cent. Consider prophylactic EEG monitoring if his GCS does not improve (non-convulsive seizures). Treat clinical seizures with levetiracetam or valproate.
3. Cerebral oedema and raised ICP: His opening pressure is already 30 cm. Monitor for further deterioration. Head elevation to 30 degrees; consider hypertonic saline or mannitol if signs of herniation.
4. Sensorineural hearing loss: Arrange formal audiometry before discharge and at 6 weeks. Pneumococcal meningitis has a 10 to 30 per cent risk; dexamethasone reduces it.
5. Cognitive impairment: Assess at 3 to 6 months; neuropsychological testing if deficits persist.
6. Venous sinus thrombosis: Suspect if focal neurology develops; diagnose with MR or CT venography. [1]

SAQ 2 — HSV Encephalitis: Diagnostic Reasoning and Management (10 marks)

Prompt: A 38-year-old woman presents with 4 days of fever, headache, progressive confusion, and a single generalised seizure. MRI shows T2/FLAIR hyperintensity in the left temporal lobe. CSF shows 120 lymphocytes, 300 red blood cells, normal glucose, protein 0.9 g/L. HSV PCR is pending. Outline the diagnostic reasoning, the immediate management, and how you would interpret the PCR result. [1]

Model Answer

Diagnostic reasoning (3 marks): [1]

The clinical picture is highly suggestive of HSV encephalitis — fever, altered mental status, seizures, and characteristic temporal lobe signal change on MRI. The CSF shows a lymphocytic pleocytosis with red blood cells (haemorrhagic component), which is typical of the haemorrhagic necrosis of HSV encephalitis but not of viral meningitis. Normal glucose and mildly raised protein are consistent. This is a clinical diagnosis supported by MRI and CSF findings; the HSV PCR is confirmatory but must be interpreted in context [4].

The differential includes other viral encephalitides (VZV, enterovirus, arboviruses), autoimmune encephalitis (especially anti-NMDAR, anti-LGI1), and brain abscess — but the temporal lobe MRI pattern and haemorrhagic CSF favour HSV. [1]

Immediate management (4 marks): [1]

• Start aciclovir 10 mg/kg IV every 8 hours immediately — do not wait for the PCR. Untreated HSV encephalitis has mortality over 70 per cent; aciclovir reduces mortality to 20 to 30 per cent. The risk of treating a patient without HSV is far lower than the risk of not treating one with HSV.
• Dose-adjust for renal function — check creatinine; aciclovir is nephrotoxic (crystallises in renal tubules). Ensure adequate hydration.
• Add empiric bacterial cover (ceftriaxone + vancomycin) if bacterial meningitis cannot be excluded — but the picture is more consistent with viral encephalitis, so bacterial cover can be stopped once CSF excludes bacteria.
• Seizure management — levetiracetam or valproate for the generalised seizure; EEG to exclude non-convulsive status if GCS does not improve.
• Admit to ICU if GCS is reduced or airway compromised.
• Send the full viral multiplex PCR (HSV-1/2, VZV, enterovirus, parechovirus) and autoimmune encephalitis antibody panel (CSF and serum) — because if HSV PCR is negative, autoimmune encephalitis is the next most important treatable diagnosis [6].

Interpreting the PCR result (3 marks): [1]

• If HSV PCR is positive: HSV encephalitis confirmed. Continue aciclovir for 14 to 21 days. Stop empiric antibiotics if bacterial culture is negative.
• If HSV PCR is negative at 24 to 48 hours: Do not stop aciclovir. The HSV PCR has a sensitivity of approximately 96 to 98 per cent, but false negatives occur in the first 24 to 48 hours because the viral load is initially low [4]. Repeat the HSV PCR at 3 to 7 days. Continue aciclovir until the repeat PCR is negative and the clinical picture is consistent with an alternative diagnosis.
• If HSV PCR is repeatedly negative at 7 days and the clinical picture does not fit HSV: Stop aciclovir. Pursue alternative diagnoses — autoimmune encephalitis (send antibody panel; start empiric immunotherapy with methylprednisolone if the Graus criteria for probable autoimmune encephalitis are met) [6], VZV (treat with aciclovir; VZV PCR positive), enterovirus (supportive), or other causes.

The key principle: a single early negative HSV PCR does not exclude HSV encephalitis. The clinical and radiological picture must drive the decision to continue aciclovir. [1]