Peripheral Neuropathy in MRCP PACES: Signs, Causes and the Viva

How it presents in PACES

The classic spot diagnosis is a distal symmetrical sensorimotor polyneuropathy — a length-dependent process that starts in the feet and climbs. What walks in (or is already sitting with feet exposed) is symmetrical distal-greater-than-proximal lower-limb weakness, usually weakest at ankle dorsiflexion and toe extension, sometimes with bilateral foot drop and a high-steppage, foot-slapping gait.

Sensation is lost in a glove-and-stocking distribution that fades gradually up the limb rather than stopping at a crisp level. Reflexes are diminished or absent — the ankle jerk goes first because it is the most distal — and the plantars are flexor. Crucially there are no upper motor neurone signs: no spasticity, no clonus, no extensor plantar, no sensory level. That single set of negatives is what excludes a cord lesion and lets you commit to a peripheral, lower-motor-neurone localisation.

In Station 3 this is bread-and-butter neurology, and it also surfaces in a consultation station when a systemic clue (diabetes, alcohol, a hereditary picture) frames the presentation. Whichever station it appears in, the examiner wants to see you localise from the pattern before you reach for a cause.

Signs to look for

Run a focused checklist. These are the discriminators that earn marks:

• Symmetrical distal > proximal LMN weakness, weakest at the ankle and toes, with distal wasting (peroneal compartment, small foot muscles).
• Glove-and-stocking sensory loss that fades gradually — examine distal to proximal and note where sensation normalises. A sharp spinal level argues against neuropathy.
• Absent ankle reflexes (knee may follow if advanced) with downgoing plantars — the LMN signature.
• Separate small-fibre loss (pinprick, temperature, light touch, burning paraesthesia) from large-fibre loss (vibration, proprioception, sensory-ataxic stamping gait, Romberg positive).
• Say whether it is sensory, motor or mixed — diabetes can be any of the three, so name what you find.
• Palpate for thickened nerves: ulnar at the elbow, common peroneal at the fibular head, greater auricular in the neck, median at the wrist.
• Bedside cause-hunt: insulin marks or diabetic dermopathy (diabetes being the commonest cause in UK practice), conjunctival pallor and glossitis (B12), parotidomegaly and Dupuytren's (alcohol), a sallow uraemic tinge or dialysis access, goitre, cachexia or clubbing (paraneoplastic), a hypopigmented anaesthetic patch (leprosy), or pes cavus, clawed toes and inverted champagne-bottle legs (inherited).
• Markers of chronicity: trophic ulcers, a Charcot joint, fixed deformity.
• Offer to complete: gait, urine dipstick for glucose, a full drug and alcohol history, and an upper-limb sensory examination.

Confirming the diagnosis & differential

First ask yourself whether this is genuinely a peripheral neuropathy or a mimic. Inconsistent features should stop you: a lumbar scar or midline hair tuft (low cord or cauda equina — request a rectal examination), a urinary catheter, or an asymmetric, patchy, myotomal or dermatomal pattern. The mimics worth naming are cauda equina (myotomal loss, early sphincter and saddle involvement), a mononeuropathy, radiculopathy or plexopathy (single nerve or dermatomal), mononeuritis multiplex (patchy, two or more nerves), and B12 subacute combined degeneration or tabes — both of which would add dorsal-column or pyramidal signs and therefore upgoing plantars.

For the cause, pick one sieve and run it out loud. A workable mnemonic covers Drugs, Alcohol (and heavy metals), Metabolic (diabetes commonest, uraemia, porphyria), Infective (leprosy, HIV, Lyme), Tumour and paraneoplastic (paraprotein, anti-Hu, POEMS), B12/B6/B1 deficiency, Infiltrative (amyloid, sarcoid), Connective tissue disease (PAN, SLE, RA, Sjögren's) and Hormonal (hypothyroid, acromegaly) — plus the inflammatory (GBS, CIDP) and congenital (CMT/HMSN) categories. Treat drugs as one bucket, not a special one: isoniazid, metronidazole, nitrofurantoin, phenytoin, amiodarone, dapsone, and the platinum agents and vincristine are the usual suspects. For thickened nerves remember CHAOS: CIDP, HMSN, Acromegaly/Amyloid, Others (leprosy, sarcoid, diabetes, Refsum's).

The viva: what examiners ask

• Investigations — confirm and classify. NCS/EMG is the key test: it confirms a peripheral neuropathy and separates axonal (reduced amplitude — most acquired neuropathies, e.g. diabetes, alcohol, toxic) from demyelinating (prolonged latency, slowed conduction velocity, conduction block — flagging CIDP, GBS or CMT1).
• Staged bloods: FBC, ESR, B12/folate, U&E, LFT, fasting glucose or HbA1c, TFT, HIV serology; then serum protein electrophoresis with immunofixation (paraprotein/POEMS), ANA/ENA and ANCA, and a CXR.
• Guided third-line tests: lumbar puncture if the picture is demyelinating (albuminocytological dissociation supports GBS/CIDP), antineuronal and antiganglioside antibodies, Bence-Jones protein, and genetic testing (PMP22) if hereditary. Nerve biopsy is reserved for suspected vasculitis, amyloid or sarcoid.
• Classification — the three axes: by involvement (motor / sensory / mixed), by pathology (axonal / demyelinating / mixed), and by time course (acute / chronic).
• Management — treat the cause: glycaemic control, replace B12, stop the offending drug or toxin, alcohol cessation, correct hypothyroidism. Actively flag CIDP as the treatable demyelinating one — steroids, IVIg or plasma exchange. For neuropathic pain, use amitriptyline, duloxetine, gabapentin or pregabalin. Support with physiotherapy, AFOs or orthoses, foot care and falls and ulcer prevention.
• Complications to mention: ulceration, Charcot joint, falls, and — if autonomic involvement is suspected — postural hypotension and gastrointestinal or bladder dysfunction.

Common pitfalls / how to score

• Do not anchor on diabetes and skip the rest — name the drug, alcohol and B12 buckets aloud even when diabetes looks obvious.
• Do not miss CIDP: it is the one member of the list you can genuinely reverse.
• Do not slap on a CMT label without the inherited skeletal clues (pes cavus, clawed toes, champagne-bottle legs); short of those, keep the whole acquired differential open.
• Do not call it a cord lesion — the absence of UMN signs and any sensory level rules that out. Conversely, a back scar or hair tuft means you should request a rectal examination.
• With soft or equivocal signs (give-way power, reflexes only on reinforcement, a drifting sensory border), report honestly and qualify. Still localise to peripheral nerve from the *pattern*, and reason aloud about why the signs are inconsistent — and say that NCS/EMG will settle whether the process is length-dependent or patchy.