Peripheral Neuropathy in Older Adults — Aetiology, Clinical Features, Investigations and Management

Definition and classification. A disorder of peripheral nerves, classified by fibre type (sensory, motor, autonomic, mixed), distribution (mononeuropathy, mononeuritis multiplex, polyneuropathy, radiculopathy, plexopathy), pathology (axonal versus demyelinating) and time course (acute, subacute, chronic). Prevalence rises steeply with age — around 8–15% of people over 55.

Aetiology — mnemonic DANG THERAPIST. Diabetes; Alcohol; Nutritional (B12, thiamine, folate, vitamin E, copper); Guillain–Barré syndrome; Toxins and drugs; Hereditary (Charcot–Marie–Tooth); Endocrine and metabolic (hypothyroidism, uraemia, hepatic failure); Rheumatological and vasculitic; Amyloidosis; Paraneoplastic; Infections (leprosy, HIV, hepatitis C, Lyme); Sarcoidosis; Tumour and paraproteinaemia (MGUS, myeloma, POEMS). In India, diabetes and leprosy lead; in older adults, diabetes, B12 deficiency, alcohol, CKD, hypothyroidism, paraproteinaemia and drugs account for most cases.

Drug causes to review at every consultation. Isoniazid (always co-prescribe pyridoxine), metronidazole, nitrofurantoin, phenytoin, amiodarone, colchicine, statins, linezolid, dapsone, chloroquine, thalidomide, and chemotherapy — vincristine, cisplatin, oxaliplatin, taxanes and bortezomib. Also excess pyridoxine (a sensory ataxic neuropathy), and long-term metformin and proton-pump inhibitors acting through B12 depletion.

Clinical features. Sensory — symmetrical distal “glove-and-stocking” numbness, tingling, burning and allodynia, ascending over months to years. Motor — distal weakness and wasting, foot drop with a high-stepping gait, and loss of ankle jerks. Autonomic — postural hypotension, gastroparesis, diarrhoea or constipation, bladder dysfunction, erectile dysfunction and impaired sweating. Trophic — dry skin, foot deformity, painless ulcers and Charcot joints.

Why neuropathy matters in geriatrics. It is a major cause of falls, fractures, gait instability and loss of independence; sensory loss leads to unnoticed foot ulceration and amputation; autonomic involvement causes syncope; and neuropathic pain destroys sleep and mood. Importantly, ankle jerks and vibration sense decline physiologically with age, so isolated minor abnormalities must be interpreted with care and not over-investigated.

A structured approach — five questions. (i) What is the distribution? symmetrical distal, multifocal (mononeuritis multiplex) or proximal. (ii) Which fibres are involved? small fibre — pain and autonomic features with normal reflexes; large fibre — loss of vibration, proprioception and reflexes. (iii) Axonal or demyelinating? (iv) What is the time course? acute onset suggests Guillain–Barré syndrome, vasculitis, porphyria or a toxin. (v) Is there a systemic clue? weight loss, rash, organomegaly or a monoclonal band.

First-line investigations. Fasting and postprandial glucose and HbA1c, with an oral glucose tolerance test if these are normal — impaired glucose tolerance alone causes small-fibre neuropathy; serum vitamin B12, with methylmalonic acid or homocysteine if borderline; TSH; renal and liver function; full blood count and ESR; and serum protein electrophoresis with immunofixation, which is essential in older adults to detect a paraproteinaemia. Add HIV and hepatitis serology where indicated.

Second-line and specialist investigations. Nerve conduction studies and EMG confirm the diagnosis, localise the lesion and separate axonal from demyelinating pathology. A demyelinating pattern should prompt consideration of CIDP — a treatable cause (CSF shows albuminocytological dissociation). Further directed tests: ANA, ANCA and cryoglobulins; anti-MAG and anti-ganglioside antibodies; skeletal survey; skin biopsy for intraepidermal nerve fibre density in small-fibre neuropathy; genetic testing; and sural nerve biopsy, reserved for suspected vasculitis, amyloidosis or leprosy.

Treatment of the cause. Glycaemic control — tight but not aggressive, since hypoglycaemia is more dangerous than modest hyperglycaemia in the elderly; vitamin B12 replacement; alcohol cessation with thiamine; thyroid replacement; dialysis or transplantation for uraemia; multidrug therapy for leprosy; immunotherapy (corticosteroids, IVIG, plasma exchange) for CIDP, Guillain–Barré syndrome and vasculitic neuropathy; treatment of an underlying malignancy or paraproteinaemia; and withdrawal of the offending drug.

Symptomatic and supportive management. For neuropathic pain, first-line agents are amitriptyline or nortriptyline, duloxetine, gabapentin and pregabalin; second line, topical capsaicin 8% patch and lidocaine 5% plaster; avoid opioids for chronic neuropathic pain. Non-pharmacological care is equally important: daily foot inspection, protective well-fitting footwear, podiatry and callus/ulcer care, physiotherapy with strength and balance training, an ankle-foot orthosis for foot drop, walking aids, home hazard assessment and structured falls prevention, vitamin D and bone protection, and treatment of coexisting depression and insomnia.

AAN practice guideline on painful diabetic neuropathy (2022, reaffirmed through 2023–2025). Four drug classes have comparable efficacy — tricyclic antidepressants, SNRIs (duloxetine, venlafaxine), gabapentinoids, and sodium-channel blockers (lamotrigine, lacosamide, oxcarbazepine) — so the choice should be driven by comorbidity and adverse-effect profile rather than a fixed ladder. Critically, opioids, including tramadol, should NOT be offered for painful diabetic neuropathy. In older adults this pushes practice towards duloxetine or a reduced-dose gabapentinoid and away from amitriptyline, which appears on the AGS Beers Criteria 2023.

Two shifts in disease-modifying thinking (2023–2025). (i) Glycaemic control alone is insufficient in type 2 diabetes — the components of the metabolic syndrome (obesity, hypertriglyceridaemia, hypertension) are now recognised as independent, modifiable drivers of neuropathy, so lifestyle and lipid management form part of neuropathy treatment, not merely of cardiovascular prevention. (ii) Hereditary transthyretin amyloid polyneuropathy (ATTRv) — which classically presents in older adults as a painful small-fibre and autonomic neuropathy with cardiomyopathy and carpal tunnel syndrome — is now treatable with RNA-silencing agents (patisiran, vutrisiran) and the stabiliser tafamidis. Amyloid neuropathy must therefore be actively sought rather than assumed untreatable.