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neuro.encephalitis-anti-lgi1.v1PRODUCTION
neuro.encephalitis-anti-lgi1.v1

Anti-LGI1 Encephalitis

neurologyacutesubacuteadultgeriatric
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

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)

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Autoimmune limbic encephalitis pathway activated

Patient inputs (16)

Anti-LGI1 strongly older adult predominant (median age 60); HLA-DR7+DRB4 association ~90% (Irani Brain 2011 PMID 21416487)

Anti-LGI1 male predominance ~60% (vs anti-NMDAR female ~80%) — demographic pivot

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

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)

Subacute memory loss + behavioural change — limbic encephalitis hallmark; hippocampal MRI involvement; persistent deficit if delayed Rx

CSF + serum LGI1 IgG via cell-based assay (CBA); CSF often more sensitive than serum in LGI1; Graus 2016 criteria (PMID 26906964)

CSF — mild lymphocytic pleocytosis or normal in LGI1 (often less prominent than NMDAR); protein mildly elevated; OCB ~30%; rule out HSV PCR

HSV PCR MANDATORY to rule out HSV encephalitis (temporal lobe overlap); empiric acyclovir until result

CT chest for thymoma (~10% of anti-LGI1 paraneoplastic); less common than NMDAR teratoma but mandatory screen

MRI brain — medial temporal T2/FLAIR hyperintensity ± hippocampal volume loss; bilateral typical; PMID 20663977

New-onset seizures in older adult — autoimmune epilepsy pivot; FBDS specifically; route to neuro.status-epilepticus.core.v1 if status (rare)

MoCA baseline + serial — limbic encephalitis cognitive deficit may persist if delayed Rx

Rituximab / B-cell depletion pre-screen if refractory

HLA-DR7 + DRB4 ~90% in LGI1 (research only; not routine clinical)

Video-EEG to capture FBDS (often subtle on routine EEG — short 1-3 sec ictal pattern); confirms autoimmune epilepsy pivot

Required before cyclophosphamide / MMF / methotrexate initiation (rare in this older population but documented)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (9)

9 need judgement
  • informationalsevereclassic_older_male_faciobrachial_dystonic_seizures
    Older male (median age 60) with FBDS — short (1-3 sec) brief jerks of arm/face; pathognomonic for LGI1 (~50%); very steroid-responsive (Irani Brain 2011 PMID 21416487)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverelimbic_encephalitis_memory_dominant
    Subacute memory loss + behavioural change + hippocampal MRI T2/FLAIR — limbic encephalitis hallmark; persistent memory deficit if delayed Rx (PMID 20663977)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereshort_duration_seizures_amenable_to_steroid
    New-onset seizures in older adult dramatically responsive to high-dose IVMP — autoimmune epilepsy pivot; consider anti-LGI1 + other autoimmune AE panel (Irani Brain 2011 PMID 21416487)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverethymoma_paraneoplastic_search_ct
    Anti-LGI1 with thymoma (~10% paraneoplastic) — CT chest mandatory screen; thymectomy if found
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererapid_cognitive_decline_dementia_mimic
    Subacute rapid cognitive decline in older adult mimicking dementia — anti-LGI1 + other autoimmune AE panel must be sent; treatable dementia mimic
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererelapse_post_immunotherapy_taper
    Relapse after immunotherapy taper (~25%) — re-induce IVMP pulse + add or escalate steroid-sparing (AZA/MMF) or rituximab; slow taper protocol
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereconcurrent_nmdar_overlap_rare
    Rare concurrent anti-NMDAR + anti-LGI1 overlap — full autoimmune AE panel sent (CASPR2/GABA-B/AMPA/DPPX/mGluR5/IgLON5/Hu/Ma2/Ri/CV2)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderaterefractory_hyponatremia_siadh
    SIADH refractory hyponatremia ~60% — Na <135 + low serum osm + elevated urine osm + urine Na >40; LGI1 hypothalamic expression; route to syndrome.hyponatremia.core.v1 for management
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildhla_dr7_drb4_genetic_susceptibility
    HLA-DR7+DRB4 ~90% in anti-LGI1 — strongest HLA association in AE; research association documented (not routine clinical)
    Trigger could not be auto-evaluated — needs clinician judgement.

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RISK_STRATIFICATIONoptionalDrives severity classification
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Recommended regimen

Anti-LGI1 acute IVMP pulse + IVIG/PLEX + slow taper + steroid-sparing + SIADH + AED + thymectomy if found (Graus 2016 PMID 26906964; Irani Brain 2011 PMID 21416487)
axis: anti_lgi1_acute_pulse_chronic_steroid_sparingstep 1 - Step 1 — First-line acute IVMP pulse (high-dose; often dramatically responsive in FBDS; Irani Brain 2011 PMID 21416487)
Selected step "Step 1 — First-line acute IVMP pulse (high-dose; often dramatically responsive in FBDS; Irani Brain 2011 PMID 21416487)" — Confirmed or strongly suspected anti-LGI1 limbic encephalitis with FBDS / memory loss / SIADH
  • methylprednisolone
    first line
    corticosteroid_pulse
    1 g IV daily × 5 d • IV • daily × 5 d (max: 5 g cumulative)
    triggers: acute_anti_lgi1
    First-line acute pulse; FBDS often dramatically responsive to high-dose IVMP within days; Graus 2016 PMID 26906964
    rxcui 6902
  • IVIG
    first line
    pooled_human_IgG
    0.4 g/kg/day × 5 d (total 2 g/kg) • IV • daily × 5 d
    triggers: acute_anti_lgi1, steroid_incomplete_lgi1
    First-line combo or alternative; Titulaer 2013 PMID 23290630
    rxcui 1426680
  • plasmapheresis (PLEX)
    second line
    apheresis
    5 cycles q48h over 10 d • IV/large-bore • q2 days × 5
    triggers: severe_anti_lgi1_steroid_ivig_refractory
    Severe or steroid+IVIG-refractory; alternative to IVIG
  • prednisone
    add on
    corticosteroid_oral_taper
    60 mg PO daily × 2-4 wk then slow taper over 6-12 mo • PO • daily slow taper
    triggers: post_pulse_maintenance_lgi1
    Maintenance after IV pulse; slow taper over 6-12 mo to prevent relapse (~25%)
    rxcui 8640

outpatient playbook — drug actions (7)

  1. 1. prednisone taper continuation
    Per taper down to 5-10 mg/d then off (over 6-12 mo) • PO • daily taper
    trigger: Post-acute maintenance
    Slow taper essential
  2. 2. azathioprine maintenance
    2-3 mg/kg/d • PO • daily
    trigger: Steroid-sparing
    TPMT + CBC + LFT
  3. 3. mycophenolate mofetil
    1-3 g/d • PO • BID
    trigger: AZA-intolerant
    CBC monitoring
  4. 4. rituximab maintenance (if refractory)
    1 g IV q6 mo × 1-2 y • IV • q6 mo
    trigger: Refractory or relapsing
    RITE2 PMID 40537079
  5. 5. tolvaptan (refractory SIADH)
    15-30 mg PO daily max 30 d • PO • daily
    trigger: Refractory SIADH
    Hepatotoxicity warning
  6. 6. levetiracetam (continued)
    1000-1500 mg BID • PO • BID
    trigger: Seizure history
    Long-term AED
  7. 7. sertraline (post-encephalitis depression)
    25-200 mg PO daily • PO • daily
    trigger: PHQ-9 ≥10; caution SIADH worsening
    Common sequelae; SSRI may worsen SIADH — monitor Na

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: 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); Subacute memory loss + behavioural change + confusion ± seizures — limbic encephalitis with hippocampal involvement on MRI; Refractory hyponatremia (SIADH) — occurs in ~60% of anti-LGI1; LGI1 hypothalamic expression.

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Anti-LGI1 Encephalitis** (neuro.encephalitis-anti-lgi1.v1).
Phenotype framing: 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)
Scope: 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)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Anti-LGI1 acute IVMP pulse + IVIG/PLEX + slow taper + steroid-sparing + SIADH + AED + thymectomy if found (Graus 2016 PMID 26906964; Irani Brain 2011 PMID 21416487)** — step "Step 1 — First-line acute IVMP pulse (high-dose; often dramatically responsive in FBDS; Irani Brain 2011 PMID 21416487)".
1. methylprednisolone 1 g IV daily × 5 d IV daily × 5 d (corticosteroid_pulse, first line) — First-line acute pulse; FBDS often dramatically responsive to high-dose IVMP within days; Graus 2016 PMID 26906964
2. IVIG 0.4 g/kg/day × 5 d (total 2 g/kg) IV daily × 5 d (pooled_human_IgG, first line) — First-line combo or alternative; Titulaer 2013 PMID 23290630
3. plasmapheresis (PLEX) 5 cycles q48h over 10 d IV/large-bore q2 days × 5 (apheresis, second line) — Severe or steroid+IVIG-refractory; alternative to IVIG
4. prednisone 60 mg PO daily × 2-4 wk then slow taper over 6-12 mo PO daily slow taper (corticosteroid_oral_taper, add on) — Maintenance after IV pulse; slow taper over 6-12 mo to prevent relapse (~25%)

Setting playbook (outpatient) — Primary neurology / autoimmune encephalitis clinic q3-6 mo — relapse surveillance + DMT taper + SIADH management + cognitive rehab + comorbidity (Graus 2016 PMID 26906964)
5. prednisone taper continuation Per taper down to 5-10 mg/d then off (over 6-12 mo) PO daily taper — Post-acute maintenance (Slow taper essential)
6. azathioprine maintenance 2-3 mg/kg/d PO daily — Steroid-sparing (TPMT + CBC + LFT)
7. mycophenolate mofetil 1-3 g/d PO BID — AZA-intolerant (CBC monitoring)
8. rituximab maintenance (if refractory) 1 g IV q6 mo × 1-2 y IV q6 mo — Refractory or relapsing (RITE2 PMID 40537079)
9. tolvaptan (refractory SIADH) 15-30 mg PO daily max 30 d PO daily — Refractory SIADH (Hepatotoxicity warning)
10. levetiracetam (continued) 1000-1500 mg BID PO BID — Seizure history (Long-term AED)
11. sertraline (post-encephalitis depression) 25-200 mg PO daily PO daily — PHQ-9 ≥10; caution SIADH worsening (Common sequelae; SSRI may worsen SIADH — monitor Na)

Non-pharmacologic actions:
- Cognitive rehab + memory strategies
- Neuropsych eval q6 mo first 2 y
- Speech / occupational therapy if needed
- Pre-DMT vaccinations
- Bone health
- Driving re-evaluation
- Mental health referral if PHQ-9 ≥10

AVOID / contraindication checks:
- Paired_serum_and_CSF_LGI1_IgG_via_CBA (CSF often more sensitive than serum)
- Send_LGI1_IgG_BEFORE_immunotherapy_if_feasible (titer lowered by steroid)
- HSV_PCR_MANDATORY_to_rule_out_HSV_encephalitis_mimic
- CT_chest_thymoma_screen_mandatory (thymoma ~10% paraneoplastic)
- Slow_6_to_12_mo_steroid_taper_to_prevent_relapse (~25% relapse on rapid taper)
- SIADH_management_route_to_syndrome.hyponatremia.core.v1 (~60% anti LGI1)
- FBDS_video_EEG_capture_to_confirm_pathognomonic_pattern
- Tolvaptan_max_30_day_duration_hepatotoxicity
- Carbamazepine_HLA_B_1502_SJS_risk_in_Asian_populations
- HBV_VZV_TB_screen_before_rituximab
- Steroid_sparing_AZA_TPMT_genotype_before_initiation
- Video_EEG_to_capture_FBDS_routine_EEG_may_miss

Monitoring

Regimen monitoring:
- Daily neuro + FBDS frequency count
- MoCA baseline + serial (q-week first month then q3 mo)
- Serum Na + serum/urine osm q-shift during SIADH
- CBC + CMP + glucose + LFT during steroid
- CD19/CD20 + IgG q3-6 mo on rituximab
- AED level (CBZ levels + Na; LEV typically not levels)
- CSF LGI1 titer at 6 mo if no improvement
- CT chest at 1 y if no initial thymoma (occasional emergence)
- PHQ-9 + GAD-7 at follow-up
- CBC + LFT monthly first 6 mo on AZA/MMF
- Annual cognitive battery for 2-3 y

Setting (outpatient) monitoring:
- CBC + LFT q3-6 mo on DMT
- CD19/CD20 q3-6 mo on rituximab
- Na + serum/urine osm q-visit
- AED levels
- Annual MRI if persistent
- CT chest at 1 y
- MoCA q3 mo; neuropsych q6 mo

Follow-up plan: 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)
- Close-out criterion: Long-term plan + specialty referrals documented

Monitoring phase: 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

Disposition

Current setting: outpatient — Primary neurology / autoimmune encephalitis clinic q3-6 mo — relapse surveillance + DMT taper + SIADH management + cognitive rehab + comorbidity (Graus 2016 PMID 26906964)

Disposition criteria:
- Continue indefinite neurology + autoimmune encephalitis clinic q3-6 mo for 2-5 y
- Admit for relapse
- Discharge from chronic DMT after 2-5 y stable

Escalation triggers (move to higher acuity):
- Breakthrough FBDS or seizure → escalate AED + consider repeat IVMP pulse
- New memory loss / behaviour → ED + relapse workup
- Severe SIADH → admit + tolvaptan + endocrinology
- IgG <500 → IVIG / pause rituximab
- Severe depression / suicidality → urgent psych

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [SEVERE] Older male (median age 60) with FBDS — short (1-3 sec) brief jerks of arm/face; pathognomonic for LGI1 (~50%); very steroid-responsive (Irani Brain 2011 PMID 21416487)
- [SEVERE] Subacute memory loss + behavioural change + hippocampal MRI T2/FLAIR — limbic encephalitis hallmark; persistent memory deficit if delayed Rx (PMID 20663977)
- [SEVERE] New-onset seizures in older adult dramatically responsive to high-dose IVMP — autoimmune epilepsy pivot; consider anti-LGI1 + other autoimmune AE panel (Irani Brain 2011 PMID 21416487)

Citations

- Graus 2016 IRCNS Position Paper Autoimmune Encephalitis Criteria + Irani Lancet Neurol 2010 LGI1 original description + Irani Brain 2011 FBDS pathognomonic + Titulaer 2013 treatment outcomes + LGI1 outcomes + LGI1 cognitive [PMID:26906964](https://pubmed.ncbi.nlm.nih.gov/26906964/)
- Cited evidence (PMID 20663977) [PMID:20663977](https://pubmed.ncbi.nlm.nih.gov/20663977/)
- Cited evidence (PMID 21416487) [PMID:21416487](https://pubmed.ncbi.nlm.nih.gov/21416487/)
- Cited evidence (PMID 40537079) [PMID:40537079](https://pubmed.ncbi.nlm.nih.gov/40537079/)
- Cited evidence (PMID 23290630) [PMID:23290630](https://pubmed.ncbi.nlm.nih.gov/23290630/)

Last reconciled with current guidelines: 2026-05-22.
References
  • Graus 2016 IRCNS Position Paper Autoimmune Encephalitis Criteria + Irani Lancet Neurol 2010 LGI1 original description + Irani Brain 2011 FBDS pathognomonic + Titulaer 2013 treatment outcomes + LGI1 outcomes + LGI1 cognitive — PMID:26906964
  • Cited evidence (PMID 20663977) — PMID:20663977
  • Cited evidence (PMID 21416487) — PMID:21416487
  • Cited evidence (PMID 40537079) — PMID:40537079
  • Cited evidence (PMID 23290630) — PMID:23290630