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neuro.encephalitis-anti-lgi1.v1

Anti-LGI1 Encephalitis

neurologyacutesubacuteadultgeriatricacuteinpatientmixed
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Phase C shard-3 neuro wave-13 (2026-05-15): authored at SCAFFOLDED — no anti-LGI1-specific workup in clinical-tools-registry.ts (workup.encephalopathy covers shared scaffolding; CSF LGI1 antibody + thymoma screen + FBDS video-EEG schema-blocked). 9 phenotypes: classic_older_male_FBDS / limbic_encephalitis_memory_dominant / refractory_hyponatremia_SIADH (~60%) / short_duration_seizures_amenable_to_steroid / thymoma_paraneoplastic_search_CT (~10%) / rapid_cognitive_decline_dementia_mimic / HLA-DR7_DRB4_genetic_susceptibility (~90%) / relapse_post-immunotherapy_taper (~25%) / concurrent_NMDAR_overlap_rare. 5 setting playbooks: home (slow taper + SIADH fluid restriction + AED + cognitive rehab) → outpatient (autoimmune encephalitis clinic q3-6 mo + DMT taper + SIADH + neuropsych) → ed (STAT MRI + LP + HSV PCR + serum/CSF LGI1 + CT chest + empiric acyclovir + methylpred) → icu (rare — severe SIADH with ODS-risk Na correction + refractory status) → inpatient (complete first-line + SIADH management + thymectomy if found + cognitive rehab). 6 PMID evidence anchor: Graus 2016 IRCNS criteria (26906964) + Irani LGI1 2010 (20663977) + Irani FBDS 2011 (21416487) + LGI1 outcomes (40537079) + Titulaer 2013 (23290630) + LGI1 cognitive (20663977). Schema-blocked: calc.edss / calc.mrs / calc.gcs / workup.lgi1_antibody_panel / workup.thymoma_chest_ct / workup.fbds_video_eeg / workup.siadh_workup — not in clinical-tools-registry; surfaced in depth bundle. Critical safety: Paired serum + CSF LGI1 IgG via CBA (CSF often more sensitive); send BEFORE immunotherapy if feasible; HSV PCR MANDATORY (HSV mimic); CT chest thymoma screen mandatory (~10%); SLOW 6-12 mo steroid taper (relapse ~25% on rapid taper); SIADH ~60% — route to syndrome.hyponatremia.core.v1; tolvaptan max 30 d (hepatotoxicity); FBDS video-EEG capture (routine EEG misses); carbamazepine specifically effective in FBDS but HLA-B*1502 SJS risk in Asian populations; LEV first-line AED initially; AZA TPMT genotype before; HBV/VZV/TB pre-rituximab; ODS risk with rapid Na correction (max 8-10 mEq/L/24 h). Sibling differentiation routes to neuro.encephalitis.hsv.v1 (HSV mimic - PCR mandatory), neuro.status-epilepticus.core.v1 (FBDS pathognomonic, rare status progression), syndrome.hyponatremia.core.v1 (SIADH ~60% pivot), neuro.encephalitis-anti-nmdar.v1 (same-commit surface AB sibling, different demographics), neuro.encephalitis-autoimmune-other.v1 (same-commit other AE). Promotion to INTEGRATED requires registered LGI1 workup (workup.lgi1_antibody_panel, workup.fbds_video_eeg, workup.thymoma_chest_ct) + autoimmune AE panel cascade in clinical-tools-registry; calc.mrs/calc.gcs/calc.moca for cognitive quantification.

Entry points (9)

  • symptom
    Older male (median age 60) with faciobrachial dystonic seizures (FBDS) — short (1-3 sec) brief jerks of arm/face; pathognomonic for LGI1 (Irani Brain 2011 PMID 21416487)
    classic_older_male_faciobrachial_dystonic_seizures
  • symptom
    Subacute memory loss + behavioural change + confusion ± seizures — limbic encephalitis with hippocampal involvement on MRI
    limbic_encephalitis_memory_dominant
  • symptom
    Refractory hyponatremia (SIADH) — occurs in ~60% of anti-LGI1; LGI1 hypothalamic expression
    refractory_hyponatremia_siadh
  • symptom
    New-onset seizures in older adult highly responsive to high-dose IVMP — autoimmune epilepsy pivot
    short_duration_seizures_amenable_to_steroid
  • history
    Anti-LGI1 with rare thymoma (~10%) — CT chest screening; less paraneoplastic association than NMDAR
    thymoma_paraneoplastic_search_ct
  • symptom
    Subacute rapid cognitive decline + memory loss + behavioural — dementia mimic in older adult; autoimmune AE panel sent
    rapid_cognitive_decline_dementia_mimic
  • history
    Strong HLA-DR7 + DRB4 association (~90%) — genetic susceptibility documented
    hla_dr7_drb4_genetic_susceptibility
  • history
    Relapse after immunotherapy taper — maintenance steroid + steroid-sparing (AZA/MMF)
    relapse_post_immunotherapy_taper
  • symptom
    Rare concurrent anti-NMDAR + anti-LGI1 overlap — full autoimmune AE panel sent
    concurrent_nmdar_overlap_rare

Required inputs (16)

  • agerequired
    demographic • used at CONTEXT
    Anti-LGI1 strongly older adult predominant (median age 60); HLA-DR7+DRB4 association ~90% (Irani Brain 2011 PMID 21416487)
  • sexrequired
    demographic • used at CONTEXT
    Anti-LGI1 male predominance ~60% (vs anti-NMDAR female ~80%) — demographic pivot
  • faciobrachial_dystonic_seizuresrequired
    symptom • used at FRAME
    FBDS pathognomonic for LGI1 (~50% of cases) — short (1-3 sec) brief jerks of arm/face; easily missed or mistaken for tics; video-EEG capture; very steroid-responsive (Irani Brain 2011 PMID 21416487)
  • memory_loss_subacuterequired
    symptom • used at FRAME
    Subacute memory loss + behavioural change — limbic encephalitis hallmark; hippocampal MRI involvement; persistent deficit if delayed Rx
  • new_onset_seizuresrequired
    symptom • used at RED_FLAGS
    New-onset seizures in older adult — autoimmune epilepsy pivot; FBDS specifically; route to neuro.status-epilepticus.core.v1 if status (rare)
  • serum_sodium_with_serum_osmrequired
    lab • used at CONTEXT
    Hyponatremia (Na <135) + low serum osm + elevated urine osm + urine Na >40 = SIADH; ~60% of anti-LGI1; route to syndrome.hyponatremia.core.v1 for management
  • csf_lgi1_antibody_serum_pairedrequired
    lab • used at INITIAL_WORKUP
    CSF + serum LGI1 IgG via cell-based assay (CBA); CSF often more sensitive than serum in LGI1; Graus 2016 criteria (PMID 26906964)
  • csf_cell_count_protein_ocb_igg_indexrequired
    lab • used at INITIAL_WORKUP
    CSF — mild lymphocytic pleocytosis or normal in LGI1 (often less prominent than NMDAR); protein mildly elevated; OCB ~30%; rule out HSV PCR
  • hsv_pcr_csfrequired
    lab • used at INITIAL_WORKUP
    HSV PCR MANDATORY to rule out HSV encephalitis (temporal lobe overlap); empiric acyclovir until result
  • ct_chest_thymoma_screenrequired
    imaging • used at INITIAL_WORKUP
    CT chest for thymoma (~10% of anti-LGI1 paraneoplastic); less common than NMDAR teratoma but mandatory screen
  • mri_brain_with_gadrequired
    imaging • used at INITIAL_WORKUP
    MRI brain — medial temporal T2/FLAIR hyperintensity ± hippocampal volume loss; bilateral typical; PMID 20663977
  • video_eeg_fbds_capture
    imaging • used at INITIAL_WORKUP
    Video-EEG to capture FBDS (often subtle on routine EEG — short 1-3 sec ictal pattern); confirms autoimmune epilepsy pivot
  • hla_dr7_drb4_if_available
    history • used at CONTEXT
    HLA-DR7 + DRB4 ~90% in LGI1 (research only; not routine clinical)
  • pregnancy_test
    lab • used at TREATMENT
    Required before cyclophosphamide / MMF / methotrexate initiation (rare in this older population but documented)
  • hbv_vzv_tb_screenrequired
    lab • used at TREATMENT
    Rituximab / B-cell depletion pre-screen if refractory
  • cognitive_baseline_mocarequired
    symptom • used at RISK_STRATIFICATION
    MoCA baseline + serial — limbic encephalitis cognitive deficit may persist if delayed Rx

12-phase flow (12)

  1. 1FRAME
    Older male (median age 60) with subacute memory loss + FBDS + SIADH-prone hyponatremia + new seizures + behavioural change → suspect anti-LGI1 limbic encephalitis (Graus 2016 PMID 26906964; Irani Brain 2011 PMID 21416487)
    inputs: faciobrachial_dystonic_seizures, memory_loss_subacute
    advance: Autoimmune limbic encephalitis pathway activated
  2. 2ENTRY
    ED / neurology / outpatient — new-onset seizures + memory loss + hyponatremia in older adult → autoimmune AE workup; established on immunotherapy → relapse vs maintenance
    inputs: age, sex
    advance: Pathway selected
  3. 3CONTEXT
    Capture HLA-DR7+DRB4 if available, prior immunotherapy, thymoma history, hyponatremia history, baseline cognition, medication history (drugs that worsen SIADH — SSRIs, thiazides)
    inputs: hla_dr7_drb4_if_available, serum_sodium_with_serum_osm
    advance: LGI1-relevant context captured
  4. 4RED_FLAGS
    Status epilepticus rare in LGI1 (route to neuro.status-epilepticus.core.v1 if present); severe SIADH with Na <120 + symptoms (route to syndrome.hyponatremia.core.v1); cognitive decline with delirium → ICU rare; FBDS by themselves do not progress to status but ICU for refractory status if present
    inputs: new_onset_seizures
    actions: workup.encephalopathy
    advance: Critical seizure / SIADH triaged
  5. 5INITIAL_WORKUP
    Serum + CSF LGI1 IgG via CBA (CSF often more sensitive — Graus 2016 PMID 26906964); CSF cell count + protein + OCB + IgG index + HSV PCR (rule out HSV); STAT MRI brain with gad (medial temporal T2/FLAIR ± hippocampal volume loss); video-EEG to capture FBDS; CT chest (thymoma ~10%); CBC + CMP + glucose + LFT + UA; serum osm + urine osm + urine Na (SIADH workup if Na low)
    inputs: csf_lgi1_antibody_serum_paired, csf_cell_count_protein_ocb_igg_index, hsv_pcr_csf, mri_brain_with_gad, video_eeg_fbds_capture, ct_chest_thymoma_screen
    actions: panel.csf, panel.cbc, panel.renal, panel.lft, panel.inflammation
    advance: LGI1 antibody pending / returned + HSV PCR negative + thymoma screened
  6. 6BRANCHING_WORKUP
    If HSV PCR+ → route to neuro.encephalitis.hsv.v1; if thymoma found → thymectomy mandatory (cardiothoracic surgery); if SIADH severe → route to syndrome.hyponatremia.core.v1 + tolvaptan / fluid restriction; if anti-LGI1 negative + clinical syndrome strong → other AE panel (CASPR2/GABA-B/AMPA/DPPX/mGluR5); paraneoplastic intracellular if older + atypical
    advance: Etiology classified (LGI1 definite / thymoma found / SIADH severe / other AE)
  7. 7DIFFERENTIAL
    Anti-LGI1 encephalitis (idiopathic vs rare thymoma paraneoplastic) / HSV encephalitis (PCR pivot) / anti-NMDAR (different demographics — young female + psychiatric + teratoma) / other AE (CASPR2/GABA-B/AMPA/DPPX/mGluR5/IgLON5) / paraneoplastic intracellular (Hu/Ma2 limbic) / Hashimoto encephalopathy / CJD / Alzheimer / vascular dementia / metabolic encephalopathy / SIADH-induced encephalopathy alone / drug-induced (SSRIs, thiazides + SIADH)
    advance: Final phenotype assigned with confidence
  8. 8RISK_STRATIFICATION
    Severity at presentation (FBDS alone vs full limbic encephalitis + SIADH + cognitive decline); time to immunotherapy (delay → persistent memory deficit; PMID 40537079); refractory vs first-line responsive; thymoma association
    inputs: cognitive_baseline_moca
    actions: calc.nihss
    advance: Severity tier + treatment urgency stratified
  9. 9TREATMENT
    FIRST-LINE: IV methylprednisolone 1 g/d × 5 d (often dramatically steroid-responsive — high-dose IVMP — FBDS often resolve within days) + IVIG 0.4 g/kg/d × 5 d (total 2 g/kg) ± PLEX 5 cycles q48h. MAINTENANCE: oral prednisone 60 mg/d × 2-4 wk then slow taper over 6-12 mo + steroid-sparing (azathioprine 2-3 mg/kg/d OR MMF 1-3 g/d). REFRACTORY (rare in LGI1): rituximab 1 g IV × 2 (days 0 + 14); cyclophosphamide reserved. SIADH MANAGEMENT (~60%): fluid restriction 1-1.5 L/d, salt tablets, tolvaptan 15-30 mg/d if refractory. AED: levetiracetam first-line; carbamazepine often effective specifically in FBDS but levetiracetam preferred initial (no enzyme induction); valproate alternative. THYMOMA: thymectomy mandatory if found
    inputs: hbv_vzv_tb_screen
    advance: First-line started + SIADH + AED active + thymoma plan if found
  10. 10DISPOSITION
    Admit neurology for any first-line immunotherapy + SIADH management; rare ICU (only refractory status or severe SIADH with Na <115 + symptoms); outpatient infusion suite for chronic rituximab; multidisciplinary follow-up (neurology + endocrinology for SIADH + cognitive neuropsych)
    advance: Disposition documented
  11. 11MONITORING
    Daily neuro + FBDS count + MoCA baseline → serial; Na + serum/urine osm q-shift during SIADH; CBC + LFT + glucose during steroid; CSF re-test at 6 wk if no improvement; CD19/CD20 + IgG q3-6 mo on rituximab; surveillance for relapse on taper (~25%); annual cognitive battery
    actions: panel.cbc, panel.lft, panel.renal
    advance: Monitoring schedule documented
  12. 12FOLLOWUP
    Cognitive rehab (memory + executive deficit common — 60% have residua at 2 y); neuropsych at 3 + 6 + 12 + 24 mo; AED management if seizure history (carbamazepine effective specifically in FBDS but LEV preferred initial); slow steroid taper supervision (over 6-12 mo); SIADH follow-up + endocrinology if persistent; pre-DMT vaccinations; PHQ-9 + GAD-7 (post-encephalitis depression common)
    actions: calc.phq9
    advance: Long-term plan + specialty referrals documented