Meningitis and Encephalitis — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Ms Sarah Chen, 26 years old, marketing executive. ^[1]

Presenting complaint: Brought to the emergency department by her partner with a 5-day history of progressive behavioural change, confusion, and a generalised seizure witnessed in the department. ^[1]

History of presenting complaint: Five days ago she was noted to be anxious and withdrawn. Over the following 48 hours she developed visual hallucinations (seeing people in the room who were not there), became increasingly agitated, and stopped recognising her partner. On the day of presentation she had a generalised tonic-clonic seizure lasting 3 minutes. There was no fever initially, but she has been febrile (38.5 degrees) for the past 24 hours. No rash, no neck stiffness reported. No recent travel. No illicit drug use. ^[1]

Past history: Glandular fever at age 18. No chronic illness. Not on any regular medications. On the oral contraceptive pill. ^[1]

Examination findings (trainee elicits):

• Alert but confused, GCS 13 (E4, V3, M6). Oriented to person only.
• Temperature 38.7 degrees, heart rate 105, blood pressure 118/72, respiratory rate 18, oxygen saturation 97 per cent on room air.
• Mild neck stiffness. No petechial rash. No papilloedema on fundoscopy.
• Repetitive orofacial movements (lip-smacking, grimacing) — involuntary.
• Motor: normal tone, power 5/5 throughout, reflexes symmetric, downgoing plantars.
• Sensation intact. Coordination limited by cooperation. ^[1]

Investigations:

• FBC: white cells 11.2 (neutrophils 8.8), haemoglobin 128, platelets 210.
• Sodium 130 mmol/L (normal 135 to 145), CRP 45, glucose 6.5.
• CT head: no mass lesion, no haemorrhage.
• Lumbar puncture: opening pressure 22 cm of water, white cells 150 (lymphocytic), red blood cells 400, glucose 3.0 (serum 6.5), protein 0.9 g/L. Gram stain: no organisms. HSV PCR: pending.
• MRI brain: T2/FLAIR hyperintensity in the right medial temporal lobe with restricted diffusion. No haemorrhage.
• EEG: periodic lateralised epileptiform discharges (PLEDs) over the right temporal region. ^[1]

Candidate's structured presentation (model)

Opening statement: ^[1]

"Ms Chen is a 26-year-old marketing executive who presents with a 5-day history of progressive psychiatric disturbance, confusion, and a generalised seizure, with fever and characteristic temporal lobe signal change on MRI. She has no significant past medical history. ^[1]

Her main problems are:

1. Herpes simplex virus encephalitis — right temporal lobe signal change on MRI, PLEDs on EEG, lymphocytic and haemorrhagic CSF, with psychiatric and dyskinetic features — immediate empiric aciclovir required
2. Generalised seizure — requires anticonvulsant therapy and EEG monitoring for non-convulsive seizures
3. Hyponatraemia (sodium 130) — likely SIADH or secondary to the encephalitis; monitor and correct cautiously
4. Differential of autoimmune encephalitis (anti-NMDAR) — given the prominent psychiatric features and orofacial dyskinesias — must be evaluated and treated if HSV PCR is negative
5. Need for ICU-level monitoring for airway, seizures, and autonomic instability ^[1]

My immediate plan is to start empiric aciclovir 10 mg/kg IV every 8 hours, add empiric ceftriaxone and vancomycin until bacterial meningitis is excluded, start levetiracetam for seizure prophylaxis, admit to ICU, and investigate for autoimmune encephalitis in parallel." ^[1]

Management plan: ^[1]

1. Empiric aciclovir immediately — 10 mg/kg IV every 8 hours (dose-adjust for renal function; ensure hydration to prevent nephrotoxicity). Do not wait for the HSV PCR. Untreated HSV encephalitis has mortality over 70 per cent; aciclovir reduces mortality to 20 to 30 per cent ^[1].
2. Empiric bacterial cover — ceftriaxone 2 g IV plus vancomycin and dexamethasone until bacterial meningitis is excluded by CSF analysis. The CSF picture (lymphocytic, haemorrhagic) favours HSV over bacterial, but partially treated bacterial meningitis cannot be excluded.
3. Seizure management — levetiracetam 1 g IV load, then 500 mg twice daily. EEG monitoring for non-convulsive status epilepticus if her GCS does not improve or fluctuates.
4. ICU admission — for airway protection, seizure monitoring, and management of autonomic instability (which is common in HSV encephalitis and more so in anti-NMDAR encephalitis).
5. Investigate for autoimmune encephalitis in parallel — send a comprehensive panel of neuronal surface and intracellular antibodies (anti-NMDAR, anti-LGI1, anti-CASPR2, anti-GABA-A/B, anti-AMPA, anti-Hu, anti-Ma2) in CSF and serum. Perform a pelvic ultrasound and MRI to screen for an ovarian teratoma (the common tumour associated with anti-NMDAR encephalitis) ^[5].
6. Monitor sodium — daily; correct slowly if SIADH drives further hyponatraemia. Avoid hypo-osmolar fluids.
7. Family communication and prognosis — counsel the partner and family about the uncertain but guarded prognosis, the possibility of cognitive impairment in survivors, and the protracted recovery.

Examiner discussion questions

Q: "Her HSV PCR comes back negative at 48 hours. What do you do?" ^[1]

"I 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 of illness because the viral load in CSF is initially low ^[2]. Ms Chen has a clinical picture (psychiatric presentation, seizures, temporal lobe MRI signal change, PLEDs on EEG, haemorrhagic CSF) that is highly consistent with HSV encephalitis. I would continue aciclovir and repeat the HSV PCR at day 3 to 7. I would also broaden my workup to include the full viral multiplex PCR (VZV, enterovirus, parechovirus) and the autoimmune encephalitis antibody panel. If the repeat HSV PCR at day 7 is negative and the clinical picture remains consistent with HSV, I may consider continuing a full 14 to 21 day course of aciclovir on clinical grounds, because HSV PCR may be falsely negative in patients already on aciclovir. If autoimmune encephalitis antibodies return positive, I would add immunotherapy."

Q: "Her anti-NMDA receptor antibodies come back positive. How does this change her management?" ^[1]

"This confirms anti-NMDA receptor encephalitis, which may be occurring in parallel with or instead of HSV encephalitis. Interestingly, HSV encephalitis can trigger a secondary autoimmune encephalitis (including anti-NMDAR) in some patients, so the two conditions are not mutually exclusive. The management changes in three ways. First, I add immunotherapy — first-line is high-dose methylprednisolone (1 g IV daily for 3 to 5 days), with or without IVIG (0.4 g/kg/day for 5 days) or plasma exchange. Second, I urgently search for and remove an ovarian teratoma — pelvic ultrasound and MRI, with gynaecology referral for laparoscopic resection if found. Tumour removal dramatically improves outcome in paraneoplastic anti-NMDAR encephalitis ^[5]. Third, I plan for a protracted recovery — anti-NMDAR encephalitis often requires weeks to months of ICU and rehabilitation, and relapses can occur. Second-line immunotherapy (rituximab or cyclophosphamide) is considered if there is no response to first-line therapy within 1 to 2 weeks."

Q: "What is the significance of the orofacial dyskinesias?" ^[1]

"Orofacial dyskinesias — repetitive lip-smacking, grimacing, chewing movements — are a characteristic feature of anti-NMDA receptor encephalitis and were described in Dalmau's original case series. They result from antibody-mediated internalisation of NMDA receptors in the basal ganglia and motor cortex. Their presence, combined with the psychiatric prodrome and seizures, should prompt strong consideration of anti-NMDAR encephalitis even before the antibody results return. The Graus 2016 criteria allow a clinical diagnosis of probable anti-NMDAR encephalitis on the basis of rapid onset of at least four of six symptom groups (psychiatric, speech, seizures, movement disorder, reduced consciousness, autonomic), an abnormal EEG or CSF, and exclusion of other causes ^[4]."

Q: "What is the prognosis of HSV encephalitis, and what follow-up does she need?" ^[1]

"Even with prompt aciclovir, HSV encephalitis carries a mortality of 20 to 30 per cent and a significant morbidity. Survivors commonly have cognitive impairment — particularly anterograde memory deficits from temporal lobe damage — seizures, behavioural change, and psychiatric disturbance. At 3 to 6 months she needs a formal neuropsychological assessment, an EEG to guide anticonvulsant continuation, and an MRI to assess the extent of residual temporal lobe damage. Some patients require long-term anticonvulsant therapy. If she had anti-NMDAR encephalitis as well, the prognosis is generally more favourable with early immunotherapy and tumour removal, but recovery is often protracted over 6 to 18 months and relapses occur in approximately 12 per cent of patients. She should be followed by a neurologist with expertise in autoimmune encephalitis." ^[1]