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neuro.peripheral-neuropathy.v1

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

neurologychronicadultgeriatric
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Detailed

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

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Chronic length-dependent vs urgent atypical phenotype framed

Patient inputs (27)

Chronic length-dependent + family history + high arches/hammer toes + no acquired cause → hereditary CMT → genetic testing (AAN 2009 England PMID 19056666)

Constitutional symptoms / rash / sicca / arthralgia → vasculitic/connective-tissue/paraneoplastic/sarcoid/amyloid screen — drives the non-DSPN branch

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

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-related + thiamine/B12/B6/copper deficiency are common reversible causes; bariatric surgery / malabsorption history

Drug/toxin axis — platinum/taxane/bortezomib/vincristine (CIPN — duloxetine only positive agent, ASCO 2020 PMID 32663120), isoniazid, amiodarone, metronidazole, nitrofurantoin, B6 excess

Uraemic neuropathy; also renal drug dose-adjustment (gabapentinoids) — calc.ckd_epi_2021 drives both

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)

Pure sensory (DSPN/idiopathic/paraneoplastic ganglionopathy) vs sensorimotor (CIDP/vasculitis) vs prominent autonomic (amyloid/diabetic/paraneoplastic) — refines the cause list

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)

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 + 2-h OGTT — OGTT detects IGT missed by fasting glucose/HbA1c in ~40% of idiopathic sensory neuropathy (Smith&Singleton 2008 PMID 18195653)

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)

Serum protein electrophoresis + immunofixation (± serum free light chains, urine) — paraproteinaemic pivot: POEMS / MGUS / AL amyloid / lymphoma (AAN 2009 highest-yield triad; England PMID 19056666)

Hypothyroidism is a reversible cause; part of the second-tier metabolic screen

Uraemic neuropathy screen + renal drug dosing (gabapentinoid dose-reduction) — calc.ckd_epi_2021

DISTRIBUTION axis — length-dependent symmetric (DSPN) vs non-length-dependent/asymmetric/multifocal (mononeuritis multiplex = vasculitis/diabetes/infiltrative — URGENT immunosuppression+biopsy)

Motor involvement (proximal+distal, demyelinating-suspect) → CIDP/GBS pivot; foot drop/asymmetric → mononeuritis multiplex; pure sensory → DSPN-spectrum

Drives pain pharmacotherapy axis; refractory severe pain → escalate class/combination + screen mood/suicidality (PHQ-9/GAD-7)

TCA contraindication screen — cardiac conduction disease / recent MI / QT prolongation / glaucoma / urinary retention / elderly anticholinergic burden (STOPP)

Severe early autonomic failure + length-dependent sensory loss → hereditary/AL amyloid pivot (disease-modifying ATTR therapy); diabetic autonomic; paraneoplastic

ESR/CRP + ANA/ENA/ANCA/cryoglobulins/complement when systemic features or asymmetric pattern — vasculitic/connective-tissue branch

Albuminocytologic dissociation (high protein, normal cells) supports CIDP/GBS demyelinating pivot — route neuro.gbs.core.v1

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)

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)

CBC (macrocytosis → B12/alcohol; cytopenias → marrow/paraproteinaemia) + LFTs (alcohol/hepatic, duloxetine baseline)

Neuropathic-pain psychiatric comorbidity is high; duloxetine dual-benefits if depression; PHQ-9/GAD-7 drive class selection + monitor suicidality at refractory pain

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Severity triggers (9)

9 need judgement
  • informationallife_threateningrapidly_progressive_ascending_gbs
    Rapidly progressive ascending weakness over days-weeks + areflexia ± autonomic ± respiratory compromise → GBS — ACUTE EMERGENCY (respiratory monitoring; route neuro.gbs.core.v1)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveremononeuritis_multiplex_vasculitic
    Non-length-dependent ASYMMETRIC / multifocal stepwise sensorimotor deficit (named-nerve territories) ± systemic features — mononeuritis multiplex = vasculitic/diabetic/infiltrative — URGENT immunosuppression + nerve+muscle biopsy
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverechronic_demyelinating_cidp
    Chronic (>8 wk) progressive or relapsing PROXIMAL+distal sensorimotor weakness, demyelinating NCS, raised CSF protein → CIDP — TREATABLE (IVIG / corticosteroids / plasma exchange; EAN/PNS 2021 Van den Bergh PMID 34327760) — route
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereparaproteinaemic_pivot
    Monoclonal protein on SPEP/immunofixation/free light chains with polyneuropathy — POEMS / MGUS-associated / AL amyloid / lymphoma — expedited haematology + amyloid workup
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehereditary_attr_amyloid
    Length-dependent sensorimotor + EARLY prominent autonomic failure ± cardiomyopathy ± family history → hereditary ATTR amyloid polyneuropathy — now DISEASE-MODIFIABLE (patisiran/vutrisiran/inotersen/eplontersen/tafamidis)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererefractory_painful_dspn_psych
    Severe refractory neuropathic pain despite optimised first-line + topical, with depression/anxiety and suicidality risk — multidisciplinary pain + urgent mental-health
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatesmall_fibre_predominant
    Small-fibre predominant — burning/lancinating distal pain + autonomic (orthostatic, sudomotor, GI), preserved reflexes + NORMAL NCS; diagnose by skin biopsy IENFD ± QSART (EFNS/PNS Lauria PMID 20642627); IGT/diabetes/Sjögren/amyloid/sodium-channelopathy
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatelarge_fibre_sensory_ataxic
    Large-fibre sensory-ataxic — lost vibration+proprioception, areflexia, positive Romberg, imbalance/falls (esp. in the dark); B12/copper deficiency, paraneoplastic sensory ganglionopathy, paraproteinaemic, CIDP
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildlength_dependent_symmetric_dspn
    Length-dependent symmetric distal sensory(±motor) polyneuropathy — stocking-glove progression; commonest pattern; cause list diabetic/prediabetic/alcohol/B12/uraemic/hypothyroid/drug/idiopathic-cryptogenic (AAN 2009 England PMID 19056666)
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Neuropathic-pain pharmacotherapy — AAN 2022 painful DPN first-line classes (gabapentinoid / SNRI / TCA / Na-channel-blocker, similar efficacy — Price PMID 34965987; OPTION-DM Tesfaye 2022 PMID 36007534); comorbidity-driven selection; topical for localized; AVOID chronic opioids
axis: neuropathic_pain_pharmacotherapystep 1 - Step 1 — First-line monotherapy by comorbidity (AAN 2022 Price PMID 34965987; OPTION-DM PMID 36007534 — classes have similar efficacy)
Selected step "Step 1 — First-line monotherapy by comorbidity (AAN 2022 Price PMID 34965987; OPTION-DM PMID 36007534 — classes have similar efficacy)" — Painful DSPN warranting pharmacotherapy after / alongside treating the underlying cause
  • pregabalin
    first line
    gabapentinoid_alpha2delta
    75 mg PO BID (start 25-75 mg HS in elderly/renal) • PO • BID (max: max 300 mg/day painful DPN (600 mg/day general); renally dose-adjust)
    triggers: painful_dspn, comorbid_anxiety, comorbid_insomnia
    AAN 2022 Price 2022 PMID 34965987 first-line (level A for painful DPN); linear PK; anxiolytic/sleep benefit; special-population renal dose by CrCl: CrCl 30-60 → max 150-300 mg/day, CrCl 15-30 → max 75-150 mg/day, CrCl<15 → max 25-75 mg/day, supplemental dose after haemodialysis; geriatric — start 25-75 mg HS, sedation/oedema/fall risk (STOPP if falls); pregnancy — registry signal, avoid/specialist; opioid-combination respiratory-depression FDA warning
    rxcui 187832
  • gabapentin
    first line
    gabapentinoid_alpha2delta
    300 mg PO HS, titrate to 300-1200 mg TID (start 100 mg HS elderly/renal) • PO • TID (max: max ~3600 mg/day; renally dose-adjust (eGFR-based))
    triggers: painful_dspn, cost_sensitive, comorbid_insomnia
    AAN 2022 first-line; saturable absorption; lower cost; special-population renal dose by CrCl: CrCl 30-59 → 400-1400 mg/day divided, CrCl 15-29 → 200-700 mg/day, CrCl<15 → 100-300 mg/day, plus a post-dialysis supplemental dose; geriatric — start 100 mg HS, sedation/peripheral oedema/falls (STOPP); pregnancy/lactation — limited data, specialist; opioid-combination respiratory-depression FDA warning
    rxcui 25480
  • duloxetine
    first line
    SNRI
    30 mg PO daily × 1 wk then 60 mg daily • PO • daily (max: max 60 mg/day for painful DPN (limited benefit >60))
    triggers: painful_dspn, comorbid_depression, comorbid_anxiety, chemotherapy_induced_neuropathy
    AAN 2022 Price 2022 PMID 34965987 first-line; the ONLY agent with appropriate positive RCT evidence for established painful CIPN (ASCO 2020 Loprinzi PMID 32663120 — modest benefit, mean ~0.73-point reduction on 0-10 average-pain scale vs placebo; NO agent prevents CIPN); special-population: AVOID at eGFR<30 (renal — no dose that is safe) and in hepatic impairment / substantial alcohol use (hepatotoxicity); pregnancy — limited data, specialist risk-benefit; lactation — low relative infant dose but monitor; geriatric — start 30 mg, watch hyponatraemia/SIADH + falls; serotonin/BP/abrupt-withdrawal risk
    rxcui 72625
  • amitriptyline
    first line
    tricyclic_antidepressant
    10-25 mg PO HS, titrate by 10-25 mg q1-2 wk • PO • HS (max: max ~100-150 mg/day (lower in elderly))
    triggers: painful_dspn, comorbid_insomnia, no_cardiac_or_anticholinergic_contraindication
    AAN 2022 first-line (OPTION-DM Tesfaye 2022 PMID 36007534 — similar efficacy to pregabalin/duloxetine); special-population: CONTRAINDICATED in cardiac conduction disease/recent MI/QT prolongation; STOPP — explicitly avoid TCAs in older adults (anticholinergic burden → cognition, urinary retention, orthostatic falls); if a TCA is required in the elderly prefer nortriptyline/desipramine at the lowest dose; renal/hepatic — no specific cut-off but accumulation/sedation risk, go low-slow; pregnancy — most-studied TCA, specialist risk-benefit; baseline ECG if any cardiac risk
    rxcui 704
  • nortriptyline
    first line
    tricyclic_antidepressant
    10-25 mg PO HS, titrate • PO • HS (max: max ~100 mg/day)
    triggers: painful_dspn, tca_indicated_but_amitriptyline_anticholinergic_excess
    Secondary-amine TCA — fewer anticholinergic/sedative effects than amitriptyline; preferred TCA in older adults when a TCA is chosen; same cardiac-conduction caution
    rxcui 7531

outpatient playbook — drug actions (3)

  1. 1. treat underlying cause
    glycaemic optimisation / B12 repletion / alcohol cessation+thiamine / stop offending drug • varies • ongoing
    trigger: Reversible/modifiable cause identified
    AAN 2009 England PMID 19056666; DCCT/EDIC PMID 20150297 — single most impactful intervention
  2. 2. first-line analgesic by comorbidity
    duloxetine 30→60 mg/d (if depression/CIPN); pregabalin 75 mg BID or gabapentin titrated (if anxiety/insomnia/renal-careful); amitriptyline/nortriptyline 10-25 mg HS (if no cardiac/anticholinergic risk) • PO • per agent
    trigger: Painful DSPN
    AAN 2022 Price PMID 34965987; OPTION-DM PMID 36007534 — classes similar efficacy, select by comorbidity
  3. 3. topical for localized pain
    lidocaine 5% patch 12 h on/off or capsaicin 8% patch q3 mo • topical • per agent
    trigger: Localized pain / frail / polypharmacy / systemic intolerance
    AAN 2022 — minimal systemic exposure

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Distal symmetric numbness / tingling / "pins-and-needles" starting in toes ascending in a stocking distribution (length-dependent DSPN — AAN 2009 England PMID 19056666); Burning / lancinating / electric distal pain, allodynia (small-fibre predominant; painful DSPN — AAN 2022 Price PMID 34965987); Sensory ataxia / imbalance / falls in the dark (large-fibre proprioceptive loss — route symptom.falls.v1).

Objective

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

Assessment

**Peripheral Neuropathy (distal symmetric polyneuropathy — DSPN; acquired-causes screen)** (neuro.peripheral-neuropathy.v1).
Phenotype framing: 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
Scope: 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

No severity triggers fired against current inputs.

Plan

Regimen axis: **Neuropathic-pain pharmacotherapy — AAN 2022 painful DPN first-line classes (gabapentinoid / SNRI / TCA / Na-channel-blocker, similar efficacy — Price PMID 34965987; OPTION-DM Tesfaye 2022 PMID 36007534); comorbidity-driven selection; topical for localized; AVOID chronic opioids** — step "Step 1 — First-line monotherapy by comorbidity (AAN 2022 Price PMID 34965987; OPTION-DM PMID 36007534 — classes have similar efficacy)".
1. pregabalin 75 mg PO BID (start 25-75 mg HS in elderly/renal) PO BID (gabapentinoid_alpha2delta, first line) — AAN 2022 Price 2022 PMID 34965987 first-line (level A for painful DPN); linear PK; anxiolytic/sleep benefit; special-population renal dose by CrCl: CrCl 30-60 → max 150-300 mg/day, CrCl 15-30 → max 75-150 mg/day, CrCl<15 → max 25-75 mg/day, supplemental dose after haemodialysis; geriatric — start 25-75 mg HS, sedation/oedema/fall risk (STOPP if falls); pregnancy — registry signal, avoid/specialist; opioid-combination respiratory-depression FDA warning
2. gabapentin 300 mg PO HS, titrate to 300-1200 mg TID (start 100 mg HS elderly/renal) PO TID (gabapentinoid_alpha2delta, first line) — AAN 2022 first-line; saturable absorption; lower cost; special-population renal dose by CrCl: CrCl 30-59 → 400-1400 mg/day divided, CrCl 15-29 → 200-700 mg/day, CrCl<15 → 100-300 mg/day, plus a post-dialysis supplemental dose; geriatric — start 100 mg HS, sedation/peripheral oedema/falls (STOPP); pregnancy/lactation — limited data, specialist; opioid-combination respiratory-depression FDA warning
3. duloxetine 30 mg PO daily × 1 wk then 60 mg daily PO daily (SNRI, first line) — AAN 2022 Price 2022 PMID 34965987 first-line; the ONLY agent with appropriate positive RCT evidence for established painful CIPN (ASCO 2020 Loprinzi PMID 32663120 — modest benefit, mean ~0.73-point reduction on 0-10 average-pain scale vs placebo; NO agent prevents CIPN); special-population: AVOID at eGFR<30 (renal — no dose that is safe) and in hepatic impairment / substantial alcohol use (hepatotoxicity); pregnancy — limited data, specialist risk-benefit; lactation — low relative infant dose but monitor; geriatric — start 30 mg, watch hyponatraemia/SIADH + falls; serotonin/BP/abrupt-withdrawal risk
4. amitriptyline 10-25 mg PO HS, titrate by 10-25 mg q1-2 wk PO HS (tricyclic_antidepressant, first line) — AAN 2022 first-line (OPTION-DM Tesfaye 2022 PMID 36007534 — similar efficacy to pregabalin/duloxetine); special-population: CONTRAINDICATED in cardiac conduction disease/recent MI/QT prolongation; STOPP — explicitly avoid TCAs in older adults (anticholinergic burden → cognition, urinary retention, orthostatic falls); if a TCA is required in the elderly prefer nortriptyline/desipramine at the lowest dose; renal/hepatic — no specific cut-off but accumulation/sedation risk, go low-slow; pregnancy — most-studied TCA, specialist risk-benefit; baseline ECG if any cardiac risk
5. nortriptyline 10-25 mg PO HS, titrate PO HS (tricyclic_antidepressant, first line) — Secondary-amine TCA — fewer anticholinergic/sedative effects than amitriptyline; preferred TCA in older adults when a TCA is chosen; same cardiac-conduction caution

Setting playbook (outpatient) — Primary-care DSPN screen + phenotyping + AAN first-tier workup + treat the underlying cause + neuropathic-pain pharmacotherapy + foot-care/fall-prevention; recognise atypical/urgent features for escalation
6. treat underlying cause glycaemic optimisation / B12 repletion / alcohol cessation+thiamine / stop offending drug varies ongoing — Reversible/modifiable cause identified (AAN 2009 England PMID 19056666; DCCT/EDIC PMID 20150297 — single most impactful intervention)
7. first-line analgesic by comorbidity duloxetine 30→60 mg/d (if depression/CIPN); pregabalin 75 mg BID or gabapentin titrated (if anxiety/insomnia/renal-careful); amitriptyline/nortriptyline 10-25 mg HS (if no cardiac/anticholinergic risk) PO per agent — Painful DSPN (AAN 2022 Price PMID 34965987; OPTION-DM PMID 36007534 — classes similar efficacy, select by comorbidity)
8. topical for localized pain lidocaine 5% patch 12 h on/off or capsaicin 8% patch q3 mo topical per agent — Localized pain / frail / polypharmacy / systemic intolerance (AAN 2022 — minimal systemic exposure)

Non-pharmacologic actions:
- Foot-care education + protective footwear; route endo.diabetes-related-foot-disease.v1 if insensate/ulcer/deformity
- Fall-prevention + PT/balance training; route symptom.falls.v1 if sensory-ataxic large-fibre
- Alcohol cessation support; nutrition referral if malabsorption/bariatric
- Honest counselling on cryptogenic prognosis; set expectation of stabilisation > reversal

AVOID / contraindication checks:
- Treat_underlying_cause_first_glycaemic_optimisation_B12_repletion_stop_offending_drug_immunosuppression_for_CIDP_or_vasculitis (AAN 2009 England PMID 19056666; DCCT/EDIC PMID 20150297)
- TCA_contraindicated_in_cardiac_conduction_disease_recent_MI_QT_prolongation_uncompensated_HF; avoid_in_elderly_glaucoma_urinary_retention_anticholinergic_burden (STOPP)
- Gabapentinoid_renal_dose_adjust_by_eGFR (calc.ckd_epi_2021); gabapentinoid_plus_opioid_respiratory_depression_FDA_warning; sedation_misuse_potential
- Avoid_chronic_opioid_therapy_for_neuropathic_pain — tramadol/tapentadol_short_term_specialist_only (AAN 2022 Price PMID 34965987 anti pattern)
- Oxcarbazepine_and_carbamazepine_monitor_hyponatraemia_SIADH (check_Na, esp. elderly/diuretics); carbamazepine_HLA B*15:02_SJS_screen_in_at_risk_ancestry + enzyme_induction + marrow_suppression
- Duloxetine_avoid_eGFR<30_and_hepatic_impairment; venlafaxine_monitor_BP_dose_dependent_HTN; SNRI/TCA_withdrawal_taper
- Pregnancy_lactation_avoid_pregabalin_and_most_agents — limited_options; specialist + risk_benefit (pregabalin signal, valproate class avoided)
- Chemotherapy_induced_neuropathy_use_duloxetine_only_positive_agent + oncology_liaison_for_dose_modification (ASCO 2020 Loprinzi PMID 32663120)
- Rapidly_progressive_ascending_weakness_route_neuro.gbs.core.v1_acute_emergency_respiratory_monitoring; chronic_relapsing_demyelinating_route_CIDP_treatable
- Asymmetric_multifocal_stepwise_deficit_route_urgent_vasculitic_workup_nerve_and_muscle_biopsy_plus_immunosuppression
- Hereditary_ATTR_amyloid_confirmed_refer_for_disease_modifying_therapy (patisiran/vutrisiran/inotersen/eplontersen/tafamidis)

Monitoring

Regimen monitoring:
- Pain scale (NRS) + function + sleep at each titration step (q1-4 wk during titration)
- PHQ-9 / GAD-7 at baseline + with pain escalation; suicidality screen at refractory severe pain
- eGFR (calc.ckd epi 2021) before + during gabapentinoid use — re-dose on renal change
- Na for oxcarbazepine/carbamazepine at 2 wk + on dose change (hyponatraemia)
- LFTs + BP for duloxetine/venlafaxine; ECG before TCA if cardiac risk
- HbA1c + diabetic foot + annual neuropathy re-screen (ADA Standards of Care 2026)
- Re-NCS / re-phenotype if course atypical, progressive, or asymmetric (reconsider CIDP/vasculitis/paraneoplastic/amyloid)

Setting (outpatient) monitoring:
- Pain/function/mood (PHQ-9/GAD-7) at each titration (q1-4 wk during titration)
- eGFR for gabapentinoids; Na for oxcarbazepine/carbamazepine; LFT/BP for duloxetine/venlafaxine
- Annual diabetic foot + neuropathy re-screen (ADA 2026)

Follow-up plan: 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)
- Close-out criterion: Recovery/stabilisation documented or atypical course re-routed

Monitoring phase: 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

Disposition

Current setting: outpatient — Primary-care DSPN screen + phenotyping + AAN first-tier workup + treat the underlying cause + neuropathic-pain pharmacotherapy + foot-care/fall-prevention; recognise atypical/urgent features for escalation

Disposition criteria:
- Typical chronic DSPN — manage in primary care with neurology referral for atypical/unclear/treatable demyelinating
- Urgent pivots → escalate per escalation_triggers

Escalation triggers (move to higher acuity):
- Rapidly progressive ascending weakness + areflexia → GBS — same-day ED + neurology (route neuro.gbs.core.v1)
- Asymmetric/multifocal stepwise sensorimotor + systemic features → urgent neurology (vasculitic mononeuritis multiplex — biopsy + immunosuppression)
- Chronic progressive/relapsing demyelinating sensorimotor → neurology (CIDP — treatable)
- Monoclonal protein on SPEP/immunofixation → haematology (POEMS/MGUS/amyloid)
- New foot ulcer/Charcot in diabetic neuropathy → urgent foot pathway
- Refractory severe pain + suicidality → urgent mental-health + pain specialist

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Rapidly progressive ascending weakness over days-weeks + areflexia ± autonomic ± respiratory compromise → GBS — ACUTE EMERGENCY (respiratory monitoring; route neuro.gbs.core.v1)
- [SEVERE] Non-length-dependent ASYMMETRIC / multifocal stepwise sensorimotor deficit (named-nerve territories) ± systemic features — mononeuritis multiplex = vasculitic/diabetic/infiltrative — URGENT immunosuppression + nerve+muscle biopsy
- [SEVERE] Chronic (>8 wk) progressive or relapsing PROXIMAL+distal sensorimotor weakness, demyelinating NCS, raised CSF protein → CIDP — TREATABLE (IVIG / corticosteroids / plasma exchange; EAN/PNS 2021 Van den Bergh PMID 34327760) — route

Citations

- AAN 2009 Practice Parameter — Evaluation of Distal Symmetric Polyneuropathy (laboratory/genetic testing; England) + AAN 2022 Oral & Topical Treatment of Painful Diabetic Polyneuropathy (Price) + ADA Standards of Care in Diabetes 2026 (Ch.12 Neuropathy/Foot Care) + EAN/PNS 2021 CIDP guideline (Van den Bergh) + EFNS/PNS skin-biopsy small-fibre neuropathy (Lauria) + ASCO 2020 CIPN guideline update (Loprinzi) [PMID:19056666](https://pubmed.ncbi.nlm.nih.gov/19056666/)
- Cited evidence (PMID 34965987) [PMID:34965987](https://pubmed.ncbi.nlm.nih.gov/34965987/)
- Cited evidence (PMID 41358886) [PMID:41358886](https://pubmed.ncbi.nlm.nih.gov/41358886/)
- Cited evidence (PMID 34327760) [PMID:34327760](https://pubmed.ncbi.nlm.nih.gov/34327760/)
- Cited evidence (PMID 20642627) [PMID:20642627](https://pubmed.ncbi.nlm.nih.gov/20642627/)

Last reconciled with current guidelines: 2026-05-26.
References
  • AAN 2009 Practice Parameter — Evaluation of Distal Symmetric Polyneuropathy (laboratory/genetic testing; England) + AAN 2022 Oral & Topical Treatment of Painful Diabetic Polyneuropathy (Price) + ADA Standards of Care in Diabetes 2026 (Ch.12 Neuropathy/Foot Care) + EAN/PNS 2021 CIDP guideline (Van den Bergh) + EFNS/PNS skin-biopsy small-fibre neuropathy (Lauria) + ASCO 2020 CIPN guideline update (Loprinzi) — PMID:19056666
  • Cited evidence (PMID 34965987) — PMID:34965987
  • Cited evidence (PMID 41358886) — PMID:41358886
  • Cited evidence (PMID 34327760) — PMID:34327760
  • Cited evidence (PMID 20642627) — PMID:20642627