Phase E shard-3 neuro-sym wave (2026-05-16): authored at INTEGRATED — manifest forward-declared stub (engine_id only); NO panel/router entry (matches neuro.bell-palsy.v1 convention for new neuro INTEGRATED dossiers this shard). PRODUCTION promotion requires full manifest + RxNav-validated terminology. Diagnosis is CLINICAL by the IRLSSG five essential criteria (urge±sensation / worse at rest / relieved by movement / evening-night / not solely a mimic). Polysomnography ONLY if diagnosis unclear/atypical/refractory or OSA suspected (quantifies PLMS index for PLMD). Load-bearing secondary-cause + iron workup: serum ferritin + transferrin saturation MANDATORY in ALL patients (brain iron deficiency is the central RLS pathophysiology). Treat iron when ferritin ≤75 ng/mL (oral ferrous sulfate + vitamin C alternate-day if TSAT >20%) or TSAT <20% / ferritin ≤100 / oral inappropriate / CKD (IV ferric carboxymaltose — FCM RCT IRLS decrease 8.9 vs 4.0, CGI-I 48.3% vs 14.3%; IRLSSG iron consensus PMID 29425576; AAN 2016 Level B PMID 27856776). Management paradigm shift (AASM 2025 — newest, primary floor PMID 39324694/39324664): non-pharm + remove aggravators + iron repletion FIRST, then ALPHA-2-DELTA LIGANDS FIRST-LINE (gabapentin enacarbil STRONG; gabapentin/pregabalin conditional; dipyridamole conditional alternative) — preferred over dopamine agonists because of AUGMENTATION (the central long-term hazard — iatrogenic earlier onset/greater intensity/anatomic spread). Dopamine agonists (pramipexole/ropinirole/rotigotine) NO LONGER first-line for long-term therapy (augmentation; ICD ~17% Cornelius 2010 PMID 20120624; sleep attacks); rotigotine patch lower augmentation. Low-dose opioid (oxycodone-naloxone) for refractory/augmentation (Trenkwalder Lancet Neurol 2013 PMID 24140442 — IRLS 31.7→15.1 vs placebo 31.6→22.1). AVOID levodopa for daily therapy (highest augmentation — intermittent/PRN only — anti-pattern encoded). Augmentation is encoded as a dedicated RED_FLAGS focus + severity_trigger + contraindication_rules: on a dopaminergic agent, symptoms EARLIER/MORE-intense/SPREADING (esp. post-dose-increase) = augmentation, NOT undertreatment — do NOT increase the dose; ensure iron repleted, rotate off the dopaminergic, switch to alpha-2-delta ligand or low-dose opioid (Garcia-Borreguero 2016 PMID 27448465). Regimen axis rls_management — 4 stepwise tiers with curl-verified RxCUIs (RxNav forward+reverse 2026-05-16): Step 1 iron repletion + non-pharm + remove aggravators (ferrous sulfate 24947 / ferric carboxymaltose 1433693 / iron sucrose 24909) → Step 2 alpha-2-delta first-line (gabapentin enacarbil 1101333 / gabapentin 25480 / pregabalin 187832 / dipyridamole 3521 emerging) → Step 3 dopamine agonist limited (rotigotine 616739 patch preferred / pramipexole 746741 / ropinirole 72302 / carbidopa-levodopa 103990 intermittent-only anti-pattern) → Step 4 low-dose opioid refractory (naloxone/oxycodone 1545902 / methadone 6813 / tramadol 10689 caution-can-augment / clonazepam 2598 adjunct). bupropion 42347 = RLS-neutral antidepressant for depression comorbidity. Special populations: pregnancy (very common 3rd trimester, usually remits postpartum — iron/folate + non-pharm first, most drugs avoided, OB co-managed), CKD/ESRD/dialysis (high prevalence — IV iron preferred + renal-adjusted gabapentinoid; route neph.ckd.core.v1), elderly (dopamine-agonist sleep-attacks/falls + gabapentinoid sedation/falls STOPP — dose-reduce; route symptom.falls.v1), iron-deficiency/IDA (route heme.iron-deficiency-anemia.core.v1 — shipped this shard), depression comorbidity (avoid mirtazapine/SSRI/SNRI worsening — use bupropion). Sibling differentiation: neuro.peripheral-neuropathy.v1 (key mimic + secondary contributor — pivot: relief by movement + circadian vs sensory loss), heme.iron-deficiency-anemia.core.v1 (iron central — overt IDA/GI-loss route; cross-referenced repletion algorithm), neph.ckd.core.v1 (CKD/ESRD secondary RLS), symptom.falls.v1 (DA/gabapentinoid fall risk in elderly — STOPP). All shipped this shard. Schema-blocked downstream: calc.irls (IRLS/IRLSSG Rating Scale 10-item 0-40 severity), calc.augmentation_severity (ASRS), workup.restless_legs (dedicated RLS branching) — NOT in clinical-tools-registry; severity encoded NARRATIVELY in flow + severity_triggers; workup.insomnia is the resolving entry workup (RLS is a major sleep-disruptor; AASM insomnia card explicitly evaluates RLS). Surfaced in research bundle schema-blocked queue. Evidence: 10 WebSearch-verified PMIDs (2026-05-16). PMID corrections vs task brief: IRLSSG iron consensus 29773288→29425576 (Allen 2018 Sleep Med); Allen NEJM pregabalin/pramipexole 24450891→24521108. AASM 2025 (PMID 39324694) adopted as the newest primary guideline floor per always-latest rule; AAN 2016 (27856776) retained as the older anchor. DEPTH-PASS-2 (2026-05-18, shard-3 CL-3): added the §5.5.2 Bayesian differential layer (prisma/seed/ros-and-ddx/neuro.restless-legs.v1.{ros,differentials,finding-lrs}.ts — auto-registered by readdir): 12 ROS items (the 5 IRLSSG essential criteria + supportive features [first-degree FHx, PLMS index, dramatic dopaminergic response] + iron/augmentation/ICD/aggravating-drug pivots), 10 differentials with sourced pre-test priors (RLS/WED, nocturnal leg cramps, peripheral neuropathy [→ neuro.peripheral-neuropathy.v1], drug-induced akathisia, positional discomfort/ischaemia, PLMD, chronic venous insufficiency, arthritis/joint pain, myelopathy/radiculopathy [→ neuro.peripheral-neuropathy.v1], iron-deficient/iron-responsive RLS [→ heme.iron-deficiency-anemia.core.v1 / neph.ckd.core.v1]), and 27 finding×diagnosis LR rows. RLS-defining cardinal criteria (1 urge / 3 movement-relief / 4 circadian / 5 not-solely-a-mimic) carry distinct LR+ ≥15 with strongly discriminating LR- (≤~0.1). Iron studies converted to LR by arithmetic from the IRLSSG iron consensus (PMID 29425576): ferritin ≤75 ng/mL LR+ ≈ 0.70/0.25 ≈ 2.8 (LR- ≈ 0.40); TSAT <20% LR+ ≈ 0.55/0.10 ≈ 5.5 (LR- ≈ 0.50). Two conditional-dependency notes encoded: (#A) ferritin-threshold LR | inflammation/CRP — ferritin is an acute-phase reactant so rely on TSAT (not ferritin) in inflammation/CKD and do NOT multiply the two iron LRs; (#B) urge-criterion LR | circadian-timing — the criterion-1 urge LR is gated by criterion-4 circadian context, so score the 5 criteria as a JOINT gate not 5 independent multiplicative LRs. §5.5.1 depth-pass-2 quantitative tightening (additive, schema-preserving): ≥10 distinct effect-size numbers with units + inline trial/year/PMID are now wired into severity_triggers and notes — pregabalin vs pramipexole 0.5 mg augmentation 7.7%→2.1% over 40-52 wk (Allen NEJM 2014 PMID 24521108); cumulative augmentation ~5-8%/yr, up to ~40-70% over years on levodopa/short-acting DA (Garcia-Borreguero 2016 PMID 27448465); ICD ~17% on dopaminergic RLS therapy (9% shopping / 11% eating / 5% gambling / 3% hypersexuality / 7% punding; Cornelius 2010 PMID 20120624); prolonged-release oxycodone-naloxone IRLS 31.7→15.1 vs placebo 31.6→22.1 at wk 12 (n=304; Trenkwalder Lancet Neurol 2013 PMID 24140442); IV ferric carboxymaltose IRLS decrease 8.9 vs 4.0, CGI-I 48.3% vs 14.3% (corroborated PMID 28643901); iron-treatment thresholds ferritin ≤75 ng/mL / TSAT <20% / ferritin ≤100 (IRLSSG iron consensus PMID 29425576); recheck ferritin/TSAT 8-12 wk; pregnancy 3rd-trimester ~2-3× prevalence with usual postpartum remission (Silber 2021 PMID 34218864). Explicit AUGMENTATION-DEPRESCRIBING trigger added as DATA (cross-taper OFF dopamine agonist over 1-2 wk → alpha-2-delta / low-dose oxycodone-naloxone; do NOT up-titrate). Quantified special-population branches added: pregnancy (low-dose iron+folate+non-pharm first, AVOID dopamine agonists/gabapentinoids in pregnancy as data, opioid only if severe + OB/specialist co-managed), renal/ESRD (IV iron + renal-adjusted gabapentin enacarbil — avoid if CrCl <30; route neph.ckd.core.v1), geriatric (ICD ~17% + gabapentinoid/DA fall risk STOPP — lowest effective dose, prefer rotigotine patch, avoid clonazepam; route symptom.falls.v1). Resolving cross-dossier engine_id routes (≥2): symptom.falls.v1 and neph.ckd.core.v1 (also neuro.peripheral-neuropathy.v1 and heme.iron-deficiency-anemia.core.v1 wired in §5.5.2 differentials via linked_disease_engine). last_reconciled bumped 2026-05-16 → 2026-05-18; no calc.* ids added (IRLS/ASRS remain schema-blocked, narrative-encoded); no drug codes added or changed. DEPTH-PASS-3 2026-05-26 (lane-E): +NMA +USPSTF +Cochrane +ICER stubs +decision thresholds, side-car at neuro.restless-legs.v1._depth-pass-3.md.