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neuro.peripheral-neuropathy.v1

Peripheral Neuropathy (distal symmetric polyneuropathy — DSPN; acquired-causes screen)

neurologychronicadultgeriatricoutpatientinpatienttransition
Start encounter →Print handoutPRODUCTION

Phase C shard-3 neuro expansion (2026-05-16): authored at INTEGRATED tier — manifest file forward-declared (stub manifest in prisma/seed/manifests permits pointer resolve; PRODUCTION promotion requires full manifest + RxNav-validated terminology + LOINC backfill confirmation). NO panel file (matches in-shard neuro.bell-palsy.v1 precedent — new neuro INTEGRATED dossiers have no router entry this shard). Phenotyping is the load-bearing Bayesian branch: TEMPORAL (acute<4wk GBS-emergency / subacute / chronic DSPN-CIDP-hereditary) × DISTRIBUTION (length-dependent symmetric DSPN vs non-length-dependent asymmetric/multifocal = mononeuritis multiplex = vasculitis-urgent) × FIBRE-TYPE (large: numbness/imbalance/areflexia/proprioception vs small: burning/autonomic/normal-NCS → skin biopsy IENFD/QSART Lauria PMID 20642627) × MOTOR/SENSORY/AUTONOMIC × DEMYELINATING/AXONAL (NCS/EMG). Each pattern → distinct cause list + next test. AAN 2009 highest-yield first-tier (England PMID 19056666): HbA1c/fasting glucose + 2-h OGTT (IGT accounts for ~40% of otherwise-idiopathic sensory neuropathy — Smith&Singleton 2008 PMID 18195653), B12 with metabolites (MMA±homocysteine), SPEP+immunofixation (POEMS/MGUS/amyloid); plus TSH, renal, CBC/LFT. Routine extensive panels low-yield without phenotype-direction. CMT genetic testing if chronic length-dependent + family history + no acquired cause. 9 phenotype severity_triggers: length-dependent symmetric DSPN / small-fibre predominant / large-fibre sensory-ataxic / mononeuritis-multiplex vasculitic (URGENT) / rapidly-progressive ascending GBS (LIFE-THREATENING emergency) / chronic demyelinating CIDP (treatable — route) / paraproteinaemic (POEMS/MGUS/amyloid) / hereditary ATTR amyloid (now disease-modifiable) / refractory painful DSPN with psych+suicidality. 4 setting playbooks: outpatient primary-care (screen + phenotype + first-tier workup + treat cause + pain pharmacotherapy + foot/fall) → outpatient specialist neurology (NCS/EMG + skin biopsy + directed second-tier + disease-modifying CIDP/vasculitis/ATTR) → inpatient (urgent pivots GBS/vasculitis/paraprotein) → transition (post-urgent-admission handoff). 2 regimen axes: neuropathic_pain_pharmacotherapy (4-step — first-line gabapentinoid/SNRI/TCA-by-comorbidity → alt-first-line+Na-channel-blocker+combination per OPTION-DM PMID 36007534 → topical capsaicin8%/lidocaine5% → constrained tramadol/tapentadol short-term-only with explicit chronic-opioid anti-pattern; AAN 2022 Price PMID 34965987) and np_disease_modifying_underlying (glycaemic optimisation DCCT/EDIC PMID 20150297 + B12/thiamine repletion + ATTR disease-modifying patisiran/vutrisiran/inotersen/eplontersen/tafamidis). All non-first_line drugs carry non-empty triggers; all pharmacologic drugs RxNav-curl-validated. Sibling differentiation maps to neuro.gbs.core.v1 (GBS-emergency + CIDP-treatable demyelinating pivot — single most important), heme.b12-folate-deficiency-anemia.core.v1 (B12 myeloneuropathy — reversible, just shipped this shard), endo.dm2.core.v1 (glycaemic optimisation — single most modifiable factor + IGT/prediabetes), endo.diabetes-related-foot-disease.v1 (insensate foot/ulcer/Charcot), symptom.falls.v1 (large-fibre sensory ataxia fall risk), symptom.weakness.ed.v1 (undifferentiated acute-weakness triage) — 6 cross-refs, all resolving in-shard. Schema-blocked downstream calculators (NOT in clinical-tools-registry — encoded narratively + queued in depth bundle, NO fake calc ids added): calc.dn4 (DN4 neuropathic-pain screen, cut-off ≥4), calc.mnsi (Michigan Neuropathy Screening Instrument), calc.uens (Utah Early Neuropathy Scale — small-fibre), calc.mtcns (modified Toronto Clinical Neuropathy Score), calc.tcss (Toronto Clinical Scoring System), calc.nis_ll (Neuropathy Impairment Score lower-limb), calc.npsi (Neuropathic Pain Symptom Inventory). Surfaced via calc.phq9/calc.gad7/calc.ckd_epi_2021 (registry-resolving) for pain-mood comorbidity + renal drug dosing. Critical safety: ALWAYS phenotype before labelling idiopathic — asymmetric/multifocal = vasculitic (urgent biopsy+immunosuppression), rapidly progressive ascending = GBS (route emergency), demyelinating chronic = CIDP (treatable, route), paraprotein = POEMS/amyloid (haematology). TREAT THE UNDERLYING CAUSE first (glycaemic/B12/alcohol/drug/immunotherapy/ATTR). AVOID chronic opioids (AAN 2022 anti-pattern). TCA contraindicated in cardiac conduction disease/elderly anticholinergic; gabapentinoid renal dose-adjust + opioid respiratory-depression FDA warning; oxcarbazepine/carbamazepine hyponatraemia; duloxetine hepatic/eGFR<30. Depth-pass-2 (2026-05-18, shard-3 / CL-3): added the §5.5.2 Bayesian differential layer as net-new ros-ddx seeds (prisma/seed/ros-and-ddx/neuro.peripheral-neuropathy.v1.{ros,differentials,finding-lrs}.ts — auto-registered by seed-ros-and-ddx.ts readdir): 12 phenotyping ROS items, 9 terminal-phenotype differentials each with a sourced prospective/population pre-test prior (length-dependent DSPN, small-fibre, CIDP, GBS, vasculitic mononeuritis multiplex, paraproteinaemic, hereditary CMT/ATTR, B12/copper, alcohol/toxic), and 30 finding×diagnosis LR rows (24 LR+ discriminators / 30 carrying LR−; ≥4 conditional-dependency notes — NCS|demyelinating-vs-axonal, OGTT|fasting-glucose-normal, IENFD|NCS-normal, MMA|B12-low; named pivot per look-alike pair DSPN/CIDP/GBS/MM/B12). LR operating characteristics from primary literature with explicit sens/spec→LR arithmetic in comments: Perkins 2001 Diabetes Care PMID 11213874 (n=478 vs NCS — vibration on-off LR+ 26.6/LR− 0.33, 10 g monofilament LR+ 10.2/LR− 0.34, superficial pain LR+ 9.2/LR− 0.50), Wang 2017 monofilament meta PMID 29119118 (pooled sens 0.53/spec 0.88 → LR+ 4.5/LR− 0.53), Lauria EFNS/PNS IENFD PMID 20642627 (spec 95-97%/sens 45-80% → conservative LR+ 13.0/LR− 0.37), AAN 2009 England PMID 19056666 (B12 MMA elevated 98.4% vs homocysteine 95.9%), EAN/PNS 2021 CIDP PMID 34327760, Smith&Singleton 2008 PMID 18195653, Kyle 2006 MGUS population study PMID 16571879. §5.5.1 quantitative tightening (additive, schema-preserving): DCCT/EDIC PMID 20150297 wired with explicit RRR ~60% + EDIC 22% vs 28% (ARR ~6pp, NNT ~17), OPTION-DM PMID 36007534 combination ~1.0-point NRS delta, ASCO 2020 PMID 32663120 duloxetine ~0.73-point CIPN reduction, Smith 2006 PMID 16732011 IENFD +1.4±2.3 fibre/mm p<0.004, plus structured renal-CrCl/geriatric-STOPP/pregnancy special-population data on pregabalin/gabapentin/amitriptyline/duloxetine. Guideline-delta check (WebSearch 2026-05-18): AAN 2009 DSP evaluation REAFFIRMED Feb 2025 and AAN DSP case-definition reaffirmed Oct 2024 — both still current, no substantive change vs the existing research bundle. No RxCUI/drug code added or changed (all pharmacotherapy unchanged). All 6 cross-ref engine_ids resolve in-shard. DEPTH-PASS-3 2026-05-26 (lane-E): +NMA +USPSTF +Cochrane +ICER stubs +decision thresholds, side-car at neuro.peripheral-neuropathy.v1._depth-pass-3.md.

Entry points (9)

  • symptom
    Distal symmetric numbness / tingling / "pins-and-needles" starting in toes ascending in a stocking distribution (length-dependent DSPN — AAN 2009 England PMID 19056666)
    distal_numbness_tingling
  • symptom
    Burning / lancinating / electric distal pain, allodynia (small-fibre predominant; painful DSPN — AAN 2022 Price PMID 34965987)
    burning_neuropathic_pain
  • symptom
    Sensory ataxia / imbalance / falls in the dark (large-fibre proprioceptive loss — route symptom.falls.v1)
    gait_imbalance_falls
  • symptom
    Asymmetric / multifocal stepwise sensorimotor deficit (mononeuritis multiplex — vasculitic/diabetic/infiltrative — URGENT)
    asymmetric_stepwise_deficit
  • symptom
    Rapidly progressive ascending weakness over days-weeks ± areflesia (GBS — acute emergency; route neuro.gbs.core.v1)
    rapidly_progressive_ascending_weakness
  • symptom
    Chronic (>8 wk) progressive or relapsing proximal+distal sensorimotor weakness (CIDP — treatable; route)
    chronic_progressive_relapsing_sensorimotor
  • symptom
    Orthostatic dizziness / early satiety / erectile dysfunction / sudomotor change (autonomic + small-fibre — amyloid/diabetic/paraneoplastic)
    autonomic_symptoms
  • lab_abnormality
    Incidental low B12 / elevated HbA1c / monoclonal protein on a metabolic screen with subtle sensory symptoms
    incidental_b12_low_or_a1c_high
  • problem_list
    Known diabetes presenting for neuropathy screen / new foot symptoms (ADA Standards of Care 2026 annual screen)
    diabetes_with_foot_symptoms

Required inputs (27)

  • agerequired
    demographic • used at CONTEXT
    DSPN prevalence rises with age; hereditary CMT presents younger; idiopathic cryptogenic sensory neuropathy is an elderly diagnosis of exclusion; TCA/gabapentinoid dosing more conservative in geriatric
  • onset_temporal_courserequired
    symptom • used at FRAME
    TEMPORAL axis — acute <4 wk (GBS/toxic/vasculitic — urgent) vs subacute 4-8 wk vs chronic >8 wk (DSPN/CIDP/hereditary); the first phenotyping branch (AAN 2009 England PMID 19056666)
  • distribution_patternrequired
    symptom • used at RED_FLAGS
    DISTRIBUTION axis — length-dependent symmetric (DSPN) vs non-length-dependent/asymmetric/multifocal (mononeuritis multiplex = vasculitis/diabetes/infiltrative — URGENT immunosuppression+biopsy)
  • fibre_type_patternrequired
    symptom • used at DIFFERENTIAL
    FIBRE-TYPE axis — large-fibre (numbness/imbalance/areflexia/lost vibration+proprioception) vs small-fibre (burning/autonomic/preserved reflexes+NCS → skin biopsy IENFD/QSART; Lauria PMID 20642627)
  • motor_sensory_autonomic_mixrequired
    symptom • used at DIFFERENTIAL
    Pure sensory (DSPN/idiopathic/paraneoplastic ganglionopathy) vs sensorimotor (CIDP/vasculitis) vs prominent autonomic (amyloid/diabetic/paraneoplastic) — refines the cause list
  • weakness_present_and_patternrequired
    symptom • used at RED_FLAGS
    Motor involvement (proximal+distal, demyelinating-suspect) → CIDP/GBS pivot; foot drop/asymmetric → mononeuritis multiplex; pure sensory → DSPN-spectrum
  • autonomic_orthostatic_features
    symptom • used at BRANCHING_WORKUP
    Severe early autonomic failure + length-dependent sensory loss → hereditary/AL amyloid pivot (disease-modifying ATTR therapy); diabetic autonomic; paraneoplastic
  • neuropathic_pain_severityrequired
    symptom • used at TREATMENT
    Drives pain pharmacotherapy axis; refractory severe pain → escalate class/combination + screen mood/suicidality (PHQ-9/GAD-7)
  • diabetes_or_prediabetes_statusrequired
    history • used at CONTEXT
    Diabetes is the commonest cause in high-income settings (~half of DSPN); prediabetes/IGT accounts for ~40% of otherwise-idiopathic sensory neuropathy (Smith&Singleton 2008 PMID 18195653); glycaemic control modifiable (DCCT/EDIC PMID 20150297)
  • alcohol_nutrition_historyrequired
    history • used at CONTEXT
    Alcohol-related + thiamine/B12/B6/copper deficiency are common reversible causes; bariatric surgery / malabsorption history
  • neurotoxic_drug_chemo_exposurerequired
    history • used at CONTEXT
    Drug/toxin axis — platinum/taxane/bortezomib/vincristine (CIPN — duloxetine only positive agent, ASCO 2020 PMID 32663120), isoniazid, amiodarone, metronidazole, nitrofurantoin, B6 excess
  • family_history_neuropathy_foot_deformityrequired
    history • used at BRANCHING_WORKUP
    Chronic length-dependent + family history + high arches/hammer toes + no acquired cause → hereditary CMT → genetic testing (AAN 2009 England PMID 19056666)
  • systemic_features_weight_loss_rash_siccarequired
    history • used at BRANCHING_WORKUP
    Constitutional symptoms / rash / sicca / arthralgia → vasculitic/connective-tissue/paraneoplastic/sarcoid/amyloid screen — drives the non-DSPN branch
  • ckd_or_dialysis_statusrequired
    history • used at CONTEXT
    Uraemic neuropathy; also renal drug dose-adjustment (gabapentinoids) — calc.ckd_epi_2021 drives both
  • cardiac_arrhythmia_qt_anticholinergic_riskrequired
    history • used at TREATMENT
    TCA contraindication screen — cardiac conduction disease / recent MI / QT prolongation / glaucoma / urinary retention / elderly anticholinergic burden (STOPP)
  • depression_anxiety_history
    history • used at RISK_STRATIFICATION
    Neuropathic-pain psychiatric comorbidity is high; duloxetine dual-benefits if depression; PHQ-9/GAD-7 drive class selection + monitor suicidality at refractory pain
  • hba1crequired
    lab • used at INITIAL_WORKUP
    Diabetes / prediabetes screen — highest-yield first-tier test (AAN 2009 England PMID 19056666); HbA1c 5.7-6.4% = prediabetes (consider OGTT, more sensitive for IGT neuropathy)
  • fasting_glucose_or_ogttrequired
    lab • used at INITIAL_WORKUP
    Fasting glucose + 2-h OGTT — OGTT detects IGT missed by fasting glucose/HbA1c in ~40% of idiopathic sensory neuropathy (Smith&Singleton 2008 PMID 18195653)
  • vitamin_b12_with_mmarequired
    lab • used at INITIAL_WORKUP
    B12 with metabolites (MMA ± homocysteine) — second highest-yield; low-normal B12 with high MMA confirms functional deficiency / myeloneuropathy (route heme.b12-folate-deficiency-anemia.core.v1; AAN 2009 PMID 19056666)
  • spep_immunofixationrequired
    lab • used at INITIAL_WORKUP
    Serum protein electrophoresis + immunofixation (± serum free light chains, urine) — paraproteinaemic pivot: POEMS / MGUS / AL amyloid / lymphoma (AAN 2009 highest-yield triad; England PMID 19056666)
  • tshrequired
    lab • used at INITIAL_WORKUP
    Hypothyroidism is a reversible cause; part of the second-tier metabolic screen
  • creatinine_egfrrequired
    lab • used at INITIAL_WORKUP
    Uraemic neuropathy screen + renal drug dosing (gabapentinoid dose-reduction) — calc.ckd_epi_2021
  • cbc_lft
    lab • used at INITIAL_WORKUP
    CBC (macrocytosis → B12/alcohol; cytopenias → marrow/paraproteinaemia) + LFTs (alcohol/hepatic, duloxetine baseline)
  • inflammatory_autoimmune_panel
    lab • used at BRANCHING_WORKUP
    ESR/CRP + ANA/ENA/ANCA/cryoglobulins/complement when systemic features or asymmetric pattern — vasculitic/connective-tissue branch
  • csf_protein_cell_count
    lab • used at BRANCHING_WORKUP
    Albuminocytologic dissociation (high protein, normal cells) supports CIDP/GBS demyelinating pivot — route neuro.gbs.core.v1
  • ncs_emg
    imaging • used at BRANCHING_WORKUP
    Nerve conduction studies / EMG when diagnosis unclear, asymmetric, motor, rapidly progressive, or demyelinating suspected — separates axonal vs demyelinating and length- vs non-length-dependent (AAN 2009 England PMID 19056666)
  • skin_biopsy_ienfd_qsart
    imaging • used at BRANCHING_WORKUP
    Distal-leg 3-mm punch skin biopsy for intraepidermal nerve fibre density (± QSART) when small-fibre neuropathy suspected with normal NCS (EFNS/PNS Lauria PMID 20642627)

12-phase flow (12)

  1. 1FRAME
    Adult/geriatric chronic distal symmetric polyneuropathy — phenotype the neuropathy (temporal/distribution/fibre-type/motor-sensory-autonomic/demyelinating-axonal) which IS the load-bearing Bayesian branch driving the workup (AAN 2009 England PMID 19056666); identify reversible/treatable + urgent causes before labelling idiopathic
    inputs: onset_temporal_course
    advance: Chronic length-dependent vs urgent atypical phenotype framed
  2. 2ENTRY
    Primary-care neuropathy screen (ADA Standards of Care 2026 annual diabetic screen; distal numbness/burning/imbalance), incidental low B12 / high HbA1c / monoclonal protein, or referral for atypical features
    inputs: age
    advance: Pathway activated
  3. 3CONTEXT
    Diabetes/prediabetes status, alcohol/nutrition, neurotoxic drug+chemo exposure, family history+foot deformity (CMT), CKD/dialysis (uraemic + drug dosing), cardiac/QT/anticholinergic risk (TCA screen), systemic features (vasculitic/paraneoplastic), depression/anxiety
    inputs: age, diabetes_or_prediabetes_status, alcohol_nutrition_history, neurotoxic_drug_chemo_exposure, family_history_neuropathy_foot_deformity, ckd_or_dialysis_status, cardiac_arrhythmia_qt_anticholinergic_risk
    advance: Context captured
  4. 4RED_FLAGS
    Rapidly progressive ascending weakness + areflexia → GBS acute emergency (respiratory monitoring; route neuro.gbs.core.v1); asymmetric/multifocal stepwise sensorimotor → mononeuritis multiplex (vasculitic — URGENT immunosuppression + nerve/muscle biopsy); chronic progressive/relapsing demyelinating sensorimotor → CIDP (treatable — route); new foot ulcer/Charcot in diabetic neuropathy; severe autonomic failure
    inputs: onset_temporal_course, distribution_pattern, weakness_present_and_pattern
    actions: workup.gbs
    advance: Urgent pivots excluded or routed
  5. 5INITIAL_WORKUP
    AAN 2009 highest-yield first-tier (England PMID 19056666): HbA1c + fasting glucose / OGTT (OGTT for IGT — Smith&Singleton 2008 PMID 18195653), B12 with MMA, SPEP+immunofixation; plus TSH, creatinine/eGFR, CBC/LFT; bedside large-fibre (vibration 128 Hz / proprioception / reflexes) + small-fibre (pinprick/temperature) exam + 10 g monofilament (ADA 2026); reserve routine extensive panels — low-yield without phenotype-direction
    inputs: hba1c, fasting_glucose_or_ogtt, vitamin_b12_with_mma, spep_immunofixation, tsh, creatinine_egfr
    actions: workup.peripheral_neuropathy, panel.glucose_a1c, panel.cmp, panel.thyroid, panel.cbc, panel.lft, panel.renal, calc.ckd_epi_2021
    advance: First-tier screen resulted
  6. 6BRANCHING_WORKUP
    Phenotype-directed: NCS/EMG if unclear/asymmetric/motor/rapidly-progressive/demyelinating-suspected (axonal vs demyelinating); skin biopsy IENFD ± QSART if small-fibre with normal NCS (Lauria PMID 20642627); CSF if CIDP/GBS demyelinating (route neuro.gbs.core.v1); inflammatory/autoimmune panel + nerve/muscle biopsy if vasculitic; serum free light chains + fat-pad/marrow if paraprotein (POEMS/amyloid); genetic testing for CMT if hereditary phenotype; HIV/hepatitis/Lyme/heavy-metal/paraneoplastic per risk
    inputs: autonomic_orthostatic_features, family_history_neuropathy_foot_deformity, systemic_features_weight_loss_rash_sicca, inflammatory_autoimmune_panel, csf_protein_cell_count, ncs_emg, skin_biopsy_ienfd_qsart
    actions: workup.peripheral_neuropathy, workup.macrocytic_anemia, workup.gbs, panel.iron, panel.inflammation, panel.hormone, cascade.labs_command
    advance: Workup tailored to phenotype; cause assigned or cryptogenic
  7. 7DIFFERENTIAL
    Assign phenotype + cause: length-dependent symmetric DSPN (diabetic/prediabetic/alcohol/B12/uraemic/hypothyroid/drug/idiopathic-cryptogenic) / small-fibre predominant / large-fibre sensory-ataxic / non-length-dependent mononeuritis multiplex (vasculitic) / demyelinating CIDP / paraproteinaemic (POEMS/MGUS/amyloid) / hereditary CMT / ATTR amyloid / GBS (route). Honest framing: a large fraction remain cryptogenic even after a complete workup
    inputs: distribution_pattern, fibre_type_pattern, motor_sensory_autonomic_mix
    advance: Phenotype + cause (or cryptogenic) assigned
  8. 8RISK_STRATIFICATION
    Pain severity + functional impact (DN4/MNSI/UENS/mTCNS/TCSS narrative scales — schema-blocked); fall risk if large-fibre sensory ataxia (route symptom.falls.v1); foot-ulcer risk if insensate diabetic foot (route endo.diabetes-related-foot-disease.v1); PHQ-9/GAD-7 for pain-related mood comorbidity + suicidality screen at refractory pain
    inputs: neuropathic_pain_severity, depression_anxiety_history
    actions: calc.phq9, calc.gad7
    advance: Severity, functional + psych risk stratified
  9. 9TREATMENT
    TREAT THE UNDERLYING CAUSE first (glycaemic optimisation — DCCT/EDIC PMID 20150297, route endo.dm2.core.v1; B12 repletion; alcohol cessation + thiamine; stop offending drug; immunosuppression for CIDP/vasculitis; ATTR disease-modifying referral). Symptomatic neuropathic-pain pharmacotherapy AAN 2022 (Price PMID 34965987): first-line gabapentinoid / SNRI / TCA / Na-channel-blocker — similar efficacy (OPTION-DM PMID 36007534), select by comorbidity; topical capsaicin 8% / lidocaine 5% for localized; AVOID chronic opioids; foot care + fall prevention + PT
    inputs: neuropathic_pain_severity, cardiac_arrhythmia_qt_anticholinergic_risk
    advance: Cause-directed + symptomatic plan set
  10. 10DISPOSITION
    Outpatient management for typical chronic DSPN; urgent inpatient + neurology for rapidly progressive (GBS — route neuro.gbs.core.v1), vasculitic mononeuritis multiplex (immunosuppression + biopsy), new paraprotein (haematology — POEMS/amyloid); specialist neurology referral for atypical/unclear/treatable demyelinating
    advance: Disposition documented
  11. 11MONITORING
    Re-screen diabetic feet + neuropathy annually (ADA 2026); pain-scale + function + mood (PHQ-9/GAD-7) at each titration; renal/hepatic monitoring for pharmacotherapy (gabapentinoid renal, duloxetine LFT); glycaemic targets; surveillance of an evolving paraprotein; re-image/re-NCS if course atypical or progressive
    inputs: neuropathic_pain_severity
    actions: calc.phq9, calc.gad7, calc.ckd_epi_2021
    advance: Monitoring plan documented
  12. 12FOLLOWUP
    Interval follow-up 4-12 wk during pain titration then per stability; foot-care + fall-prevention education; expect cause-treatment to stabilise (not always reverse) DSPN; re-investigate if progressive/atypical (re-phenotype — reconsider CIDP/vasculitis/paraneoplastic/amyloid); honest counselling on cryptogenic prognosis (generally slowly progressive, not life-limiting)
    advance: Recovery/stabilisation documented or atypical course re-routed