Makindo Medical Notes

Related Subjects: |Anti-NMDA (NMDAR) receptor encephalitis |Herpes Simplex Encephalitis (HSV) |Acute Encephalitis |Limbic Encephalitis |Paraneoplastic Limbic Encephalitis (Dementia) |Hashimoto's (Steroid responsive) Encephalopathy |Acute Disseminated Encephalomyelitis

Limbic encephalitis (LE) is an inflammatory encephalitis targeting the limbic system (hippocampi, amygdala, cingulate). It presents subacutely (<3 months) with memory impairment, psychiatric/behavioural change, and seizures. Causes include autoimmune (paraneoplastic or non-paraneoplastic) and infectious (notably HSV). Early recognition and treatment (while ruling out infection) improves outcomes.

🔎 Clinical Hallmarks

• Memory: prominent anterograde amnesia; disorientation.
• Psychiatric/behavioural: anxiety, agitation, psychosis, mood lability.
• Seizures: temporal lobe focal seizures; faciobrachial dystonic seizures (FBDS) suggest LGI1.
• Autonomic: SIADH-related hyponatraemia (classically LGI1), tachy/bradyarrhythmias.
• Movement disorders: orofacial dyskinesias, chorea (notably anti-NMDAR).
• Sleep disturbance: insomnia/parasomnias (LGI1/CASPR2).

🧠 Aetiology & Antibody Biology

Key concept: Antibodies to cell-surface/synaptic targets typically respond well to immunotherapy; antibodies to intracellular (onconeuronal) antigens are often paraneoplastic T-cell–mediated and respond less well.

🦠 Infectious Mimic

• HSV-1 encephalitis: indistinguishable early; treat empirically with IV aciclovir while awaiting CSF PCR. MRI often medial temporal hyperintensity with diffusion restriction; CSF lymphocytosis, ↑protein.

🧾 Diagnostic Approach (Graus criteria informed)

• Subacute onset (≤3 months) of memory disturbance/psychiatric symptoms/seizures plus supportive tests.
• MRI brain: T2/FLAIR hyperintensity in medial temporal lobes; can be normal early.
• CSF: lymphocytosis, mild ↑protein, OCBs; send viral PCR + autoantibodies.
• EEG: temporal slowing/epileptiform discharges; “extreme delta brush” in anti-NMDAR.
• Serum & CSF antibodies: both needed; CSF critical for NMDAR sensitivity.
• Tumour search: CT CAP, pelvic/testicular US/MRI; PET if negative. Repeat 6–12-monthly up to 4 years if onconeuronal antibodies.

🧪 Suggested Investigations

• Bloods: FBC, U&E, LFT, CRP/ESR, thyroid profile, HbA1c; autoimmune screen if indicated.
• Infection: blood cultures; HIV, syphilis serology as needed.
• LP: opening pressure, cells, protein/glucose, HSV PCR, VZV PCR, bacterial culture; CSF/serum antibody panel.
• Imaging: MRI brain (DWI/FLAIR); CT CAP ± PET for malignancy.
• EEG: detect subclinical seizures/status; temporal lobe abnormalities common.

⚕️ Management (initiate in parallel with workup)

Do not delay aciclovir if HSV is a possibility. If autoimmune LE likely, start immunotherapy early after antimicrobials.

• Empiric antivirals: IV aciclovir pending HSV PCR.
• First-line immunotherapy: IV methylprednisolone, IVIG, or plasma exchange.
• Second-line: rituximab (esp. surface Ab disease), cyclophosphamide; tocilizumab if refractory.
• Tumour treatment: urgent oncologic therapy if paraneoplastic.
• Seizure control: levetiracetam/lacosamide; minimise benzos in NMDAR unless for catatonia/rigidity.
• Autonomic/ICU care: airway protection in NMDAR; manage dyskinesias/arrhythmias.
• Hyponatraemia: often SIADH in LGI1; careful correction.
• Rehab: neuropsychology, OT/PT, psychiatric support.

📈 Prognosis

• Surface Ab LE: good recovery with therapy; memory deficits may persist.
• Onconeuronal LE: outcome depends on tumour; often partial recovery.
• HSV LE: poor without aciclovir; treat early.
• Relapses possible, esp. anti-NMDAR.

🆚 Key Differentials

• HSV encephalitis, other viral encephalitides
• Prion disease, SREAT/Hashimoto, SLE/vasculitis
• Metabolic/toxic (Wernicke’s, hepatic), glioma, neurosarcoid
• Functional (esp. early NMDAR) — maintain diagnostic humility

📌 OSCE / Viva Tips

• Say: “Subacute memory/behavioural change + seizures → rule out HSV, consider autoimmune LE; start aciclovir + arrange MRI/LP.”
• Quote Graus criteria: timecourse + MRI/CSF/EEG + exclusion of mimics.
• Drop pearls: FBDS + hyponatraemia = LGI1; psychosis/dyskinesias = NMDAR; refractory seizures = GABA_BR.
• Explain antibody biology (surface vs intracellular response).
• State tumour surveillance (6–12m intervals up to 4 yrs if onconeuronal).

🔁 Follow-Up

• Monitor cognition, mood, seizures; taper steroids carefully.
• Vaccinate before long-term B-cell therapy.
• Multi-disciplinary care: neurology, oncology, psychiatry, rehab.

📚 References

• Graus F, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016.
• Dalmau J, et al. Clinical experience & principles of immunotherapy in AE. Lancet Neurol.
• Lai M, et al. Limbic encephalitis with VGKC-complex antibodies. JNNP. 2010.