The most useful single discriminator is the time course: months to years, symmetrical, sensory and feet-first is a chronic polyneuropathy for an outpatient screen, whereas days to weeks, any weakness or any asymmetry is a different disease with a different urgency. The second is the reflexes — brisk reflexes with upgoing plantars put the lesion in the cord or brain, and sending that patient for peripheral nerve studies loses weeks. In Guillain-Barré syndrome 20–30% of patients develop respiratory failure needing ventilation during the progressive phase (Willison et al., Lancet 2016), which is why the destination is a medical admission, not a neurology clinic. Vasculitic neuropathy can cause irreversible axonal loss within days without immunosuppression. NICE NG19 separates limb- or life-threatening diabetic foot problems (immediate referral to acute services) from other active problems such as suspected Charcot arthropathy (multidisciplinary foot service within 1 working day). A paraprotein neuropathy is a recognised presentation of myeloma, MGUS, amyloidosis and Waldenström's — so in anyone aged 60 or over with persistent bone pain the NG12 myeloma tests are offered, and serum protein electrophoresis belongs in the first-line neuropathy screen at any age.

The distribution and tempo of sensory loss are the most diagnostically useful features. A length-dependent stocking-glove pattern that has crept up over years points to a metabolic, toxic or nutritional cause; asymmetric mononeuritis multiplex is vasculitis until proven otherwise; and a small-fibre neuropathy can have a normal examination and normal nerve studies, so a normal result does not mean there is no neuropathy. Identifying and removing the cause — stopping a neurotoxic drug, controlling glucose, replacing B12, reducing alcohol — matters more than any symptomatic drug. Several causes often coexist (diabetes, alcohol and a drug together), so do not stop at the first one found.

Aetiological classification directly determines treatability. Glucose control slows diabetic neuropathy, most clearly in type 1 diabetes. B12 neuropathy can be reversed if treated early, but damage becomes permanent with delay. Drug-induced neuropathy usually improves on withdrawal, and long-term nitrofurantoin prophylaxis is the example most often missed. CIDP responds to immunotherapy (IVIg or steroids) — missing it condemns the patient to progressive disability. Some neuropathies labelled idiopathic turn out to have impaired glucose tolerance, a borderline B12 or a mild hereditary neuropathy, which is why the screen is done properly once. Equally, repeated re-investigation of a stable idiopathic neuropathy is not benign: it sustains anxiety and turns up incidental findings.

The 10 g monofilament tests protective sensation, and its loss is one of the NICE NG19 risk factors that moves a person with diabetes from low to moderate or high foot risk. Loss of the ankle jerk is an early reproducible sign of a length-dependent neuropathy and should always be tested. Brisk reflexes with sensory loss indicate cord pathology, not a peripheral neuropathy — this finding needs urgent MRI spine and neurology, not a peripheral screen. Large-fibre loss (vibration, position sense, positive Romberg) predicts falls, and postural hypotension from autonomic neuropathy compounds it; both are treatable once found.

Sending the first-line panel together, rather than in waves, finds the common treatable causes in a single round and avoids months of sequential testing. NICE NG239 (2024) sets the B12 bands above and advises immediate replacement when neurological symptoms suggest deficiency, because delay risks permanent damage; methylmalonic acid helps when the result is indeterminate. The link between impaired glucose tolerance and painful small-fibre neuropathy is why an OGTT is worth doing when HbA1c is unrevealing. Serum protein electrophoresis sits in the first line rather than the second because a paraprotein changes the pathway entirely — and some IgM paraprotein (anti-MAG) neuropathies are candidates for specialist immunotherapy, a decision made in haematology or neurology.

CIDP is treatable with IVIg, steroids or plasma exchange, but only if it is recognised — so subacute or motor-predominant neuropathy goes to neurology urgently. Vasculitic neuropathy needs prompt immunosuppression to prevent irreversible axonal loss. The NG12 myeloma route runs straight through this presentation: the tests are offered in primary care and a suspected cancer referral follows if they suggest myeloma. NICE NG19 sets three different speeds for the foot — immediately to acute services for limb- or life-threatening problems, within 1 working day for other active problems, and planned foot protection service assessment for moderate or high risk — and mixing these up is how a Charcot foot is left in a shoe for weeks. Podiatry for a numb non-diabetic foot is not in NG19 but follows the same logic: the ulcer, not the numbness, is what costs the limb.

NICE CG173 (2013, updated 2020) offers amitriptyline, duloxetine, gabapentin or pregabalin as a shared decision; the local pathway sets a local order — amitriptyline, then gabapentin/pregabalin, then duloxetine (earlier for confirmed painful diabetic neuropathy) — which avoids a conflict between national and local guidance, while a clear patient-specific reason (such as side-effect profile) still justifies deviating. In painful diabetic neuropathy the OPTION-DM crossover trial (Tesfaye et al., Lancet 2022) found amitriptyline, duloxetine and pregabalin pathways gave similar pain relief, which supports choosing on tolerability. CG173 then says switch rather than combine (short cross-tapering may be needed during a switch, and any combination is specialist-led), yet stacked prescriptions accumulate: a patient arrives on amitriptyline, gabapentin and tramadol together, each under-dosed, each sedating. Titrating one agent properly and withdrawing the others usually improves both the pain and alertness. Most "failures" are under-titrated — 10 mg of amitriptyline abandoned at two weeks is not a failed trial. Standard analgesics alone are rarely effective for neuropathic pain, and tramadol is for rescue only. B12 replacement uses IM injections when neurological features are present because malabsorption (autoimmune gastritis) is the commonest cause.

Foot protection is the single highest-value intervention in sensory neuropathy: the neuropathic ulcer, not the numbness, leads to amputation, and specific prohibitions (no hot water bottles, no barefoot walking, no self-cutting of callus) change behaviour more than general advice to "look after your feet". NICE NG19 ties review frequency to risk (annual, 3–6 monthly, 1–2 monthly) and refers moderate and high risk to the foot protection service. Glucose control prevents neuropathy most clearly in type 1 diabetes (DCCT). Large-fibre sensory loss and postural hypotension both raise the falls risk, and a hip fracture in a frail patient with neuropathy carries a high mortality — so falls assessment belongs in the neuropathy review. TENS is not recommended for chronic primary pain (NG193), but neuropathic pain is a different category.

Neuropathic pain drugs are titrated over weeks, so early review is about tolerance and titration and the efficacy judgement comes at 4–6 weeks at an adequate dose — early review prevents premature abandonment. Progression of a pure sensory neuropathy to include motor features should always prompt urgent re-referral, as it may signal CIDP or vasculitic neuropathy. Annual foot risk assessment is a NICE NG19 recommendation for everyone with diabetes. B12 maintenance is lifelong in autoimmune gastritis (NICE NG239); stopping injections risks irreversible cord damage. In the SCA, the marks sit in finding every contributing cause, acting on the foot and the NG12 myeloma route, and resisting the request for "something stronger" while still offering a credible plan.