Medicine chapters
Entrapment neuropathies and multifocal neuropathy (mononeuritis multiplex)
How peripheral nerves are damaged, the common entrapment neuropathies (carpal tunnel, ulnar, radial, common peroneal, meralgia paraesthetica) and the causes and work-up of mononeuritis multiplex.
- A mononeuropathy affects one nerve; mononeuritis multiplex affects several separate nerves, usually from diabetes, vasculitis or leprosy.
- Carpal tunnel syndrome (median nerve at the wrist) gives night-time tingling of the radial 3½ fingers, positive Tinel and Phalen tests and thenar wasting; it is linked to pregnancy, hypothyroidism, RA, acromegaly and amyloid.
- Common peroneal palsy at the fibular neck gives foot drop with weak eversion but normal inversion and ankle jerk; radial palsy in the spiral groove gives wrist drop.
On this page
Overview
Peripheral nerve disease is grouped by how many nerves are involved and what part of the nerve is damaged.
- Mononeuropathy: one nerve (for example the median nerve at the wrist).
- Mononeuritis multiplex (multifocal neuropathy): two or more separate named nerves, at the same time or one after another.
- Polyneuropathy: diffuse, symmetrical, length-dependent damage starting in the feet ("glove and stocking").
- Radiculopathy (root) and plexopathy (brachial or lumbosacral plexus).
Entrapment neuropathies are common in clinics and in MCQs, and mononeuritis multiplex is a pointer to serious systemic disease such as vasculitis.
How nerves are damaged
| Mechanism | What happens | Nerve conduction finding | Examples |
|---|---|---|---|
| Demyelination | Schwann cell or myelin damage | Marked slowing of conduction, conduction block | Guillain–Barré syndrome, CIDP, hereditary (CMT type 1) |
| Axonal degeneration | The axon dies back from its far end | Conduction speed nearly normal, but small response amplitude | Toxic, metabolic, alcohol, many drugs |
| Compression / entrapment | Focal demyelination at the pinch point, some distal axon loss | Slowing across the compression site | Carpal tunnel, ulnar at elbow |
| Infarction of vasa nervorum | Nerve dies distal to the infarct (Wallerian degeneration) | Axonal pattern in individual nerves | Diabetes, polyarteritis nodosa, EGPA |
| Infiltration | Inflammatory or tumour cells in the nerve | Variable | Leprosy, sarcoidosis, lymphoma |
- Regrowth of a damaged axon is slow: up to about 1 mm a day.
- Entrapment neuropathies are more frequent in people with diabetes.
Nerve conduction studies separate demyelinating (slow velocity, conduction block) from axonal (low amplitude, near-normal velocity) neuropathy. This is the key first step in the work-up.
Common entrapment and compression neuropathies
| Nerve | Site of compression | Key features |
|---|---|---|
| Median | Carpal tunnel (under the flexor retinaculum) | Tingling of thumb, index, middle and half of ring finger; thenar (abductor pollicis brevis) wasting |
| Ulnar | Cubital tunnel (elbow); less often Guyon's canal (wrist/palm) | Claw hand, hypothenar and interossei wasting, little finger numbness |
| Radial | Spiral groove of the humerus | Wrist drop, weak brachioradialis |
| Posterior interosseous | Supinator muscle in the forearm | Finger and wrist drop, no sensory loss, brachioradialis spared |
| Lateral cutaneous nerve of thigh | Under the inguinal ligament | Meralgia paraesthetica: burning numbness of the outer thigh |
| Common peroneal (lateral popliteal) | Neck of the fibula | Foot drop, weak eversion |
| Posterior tibial | Tarsal tunnel (behind the medial malleolus) | Burning pain and numbness of the sole |
Carpal tunnel syndrome (CTS)
The commonest entrapment neuropathy: the median nerve is squeezed in the carpal tunnel.
Causes and associations (most cases are idiopathic):
- Pregnancy (third trimester), the pill, obesity.
- Hypothyroidism, acromegaly, diabetes.
- Rheumatoid arthritis and other wrist synovitis; wrist fractures or osteoarthritis.
- Amyloidosis, including β2-microglobulin amyloid in long-term dialysis patients, and AL amyloid in myeloma.
- Repetitive wrist work.
"MEDIAN TRAPP": Myxoedema, oEdema of pregnancy, Diabetes, Idiopathic, Acromegaly, Neoplasm, Trauma, Rheumatoid arthritis, Amyloid, Pregnancy/the Pill.
Symptoms and signs:
- Waking at night with pain, tingling and numbness over the thumb, index and middle fingers and the thumb side of the ring finger; shaking the hand gives relief. Pain may spread up the forearm.
- Weak grip, dropping objects.
- Wasting of the thenar eminence, weak abductor pollicis brevis (thumb abduction) and opposition.
- Tinel's sign: tapping over the carpal tunnel causes tingling in the median distribution.
- Phalen's test: holding the wrist fully flexed for about a minute reproduces symptoms.
Sensation over the thenar eminence (palm at the base of the thumb) is normal in CTS, because the median nerve's palmar cutaneous branch leaves above the wrist and runs superficial to the flexor retinaculum. Numb thenar skin points to a lesion higher up in the forearm (for example pronator syndrome).
Diagnosis: clinical, confirmed by nerve conduction studies (slowed conduction and prolonged latency across the wrist). Check TSH and glucose; consider other causes.
Management:
- Night splint holding the wrist in neutral or slight extension; treat the cause (for example thyroxine).
- Corticosteroid injection into the carpal tunnel (avoiding the nerve); often helps, may recur.
- Surgical decompression (dividing the flexor retinaculum) for persistent symptoms, wasting or nerve damage on studies.
Pregnancy-related CTS usually settles after delivery.
Ulnar neuropathy
- Commonest site: elbow (cubital tunnel), from leaning on the elbow, old elbow fracture with valgus deformity ("tardy ulnar palsy", appearing years later), or arthritis.
- Signs: claw hand (ring and little finger), wasting of hypothenar and interossei (guttering between metacarpals), weak finger abduction and adduction, Froment's sign (weak adductor pollicis, so the thumb tip flexes to grip paper), numbness of the little finger and half the ring finger.
- Guyon's canal lesions (cyclists, crutch users, tool handles) can be purely motor and spare the dorsal hand sensation, because the dorsal cutaneous branch leaves above the wrist.
- Treatment: avoid pressure on the elbow; surgical decompression or transposition if severe (results are mixed).
"Ulnar paradox": clawing is worse with a lesion at the wrist than at the elbow, because a high lesion also weakens the ulnar half of flexor digitorum profundus, so the fingers curl less.
Radial nerve palsy
- Saturday night palsy: arm hung over the back of a chair while drunk or deeply asleep; compression in the spiral groove.
- Also with midshaft humeral fractures and crutch pressure in the axilla (axillary lesions also weaken triceps).
- Signs: wrist drop, weak finger extension, weak brachioradialis; small patch of numbness on the back of the hand at the base of the thumb.
- Recovery is usual over weeks to a few months; a cock-up splint prevents contracture.
- Posterior interosseous nerve lesions give finger drop without sensory loss and with brachioradialis spared.
Common peroneal (lateral popliteal) palsy
- Compressed at the neck of the fibula: prolonged squatting or kneeling, crossing the legs, tight plaster casts, prolonged bed rest or coma, weight loss, fibular fracture. Leprosy can thicken this nerve.
- Signs: foot drop with a high-stepping gait, weak dorsiflexion and eversion, numbness of the dorsum of the foot and lateral shin.
- Inversion, plantar flexion and the ankle jerk are preserved.
- Usually recovers within months; use an ankle-foot splint meanwhile.
To tell a common peroneal palsy from an L5 root lesion: in an L5 lesion inversion (tibialis posterior) and hip abduction are also weak and there is often back pain. In common peroneal palsy, inversion is normal.
Meralgia paraesthetica
- Lateral cutaneous nerve of the thigh trapped as it passes under or through the inguinal ligament near the anterior superior iliac spine.
- Triggers: obesity, pregnancy, tight belts or trousers, diabetes.
- Purely sensory: burning, tingling or numbness over the outer thigh; no weakness and normal reflexes.
- Usually settles with weight loss and loose clothing.
Hereditary neuropathy with liability to pressure palsies (HNPP)
- Autosomal dominant deletion of the PMP-22 gene (the opposite of the duplication in Charcot–Marie–Tooth type 1A).
- Repeated pressure palsies after minor compression (peroneal, ulnar, even brachial plexus), on a background of mild neuropathy.
Mononeuritis multiplex (multifocal neuropathy)
Several individual, non-adjacent nerves are damaged, for example the ulnar nerve on one side and the common peroneal nerve on the other. The usual mechanism is infarction of the vasa nervorum (vasculitis, diabetes) or infiltration (leprosy, sarcoid, tumour). When many nerves are involved it can look like a symmetrical polyneuropathy.
Causes
| Group | Examples |
|---|---|
| Metabolic | Diabetes mellitus (the commonest overall) |
| Vasculitis | Polyarteritis nodosa (often with hepatitis B), eosinophilic granulomatosis with polyangiitis (Churg–Strauss), granulomatosis with polyangiitis, cryoglobulinaemia |
| Connective tissue disease | Rheumatoid arthritis, SLE, Sjögren syndrome |
| Infection | Leprosy (thickened nerves), HIV, hepatitis C, Lyme disease |
| Infiltration | Sarcoidosis, amyloidosis, malignancy (lymphoma, carcinoma) |
| Other | Neurofibromatosis, HNPP, multifocal motor neuropathy with conduction block |
"WARDS PLC": Wegener's (GPA), AIDS/Amyloid, Rheumatoid, Diabetes, Sarcoid/SLE, PAN, Leprosy, Carcinoma.
In Pakistan, always think of leprosy in a patient with hypopigmented, numb skin patches plus thickened nerves (ulnar at the elbow, common peroneal at the fibular neck, great auricular in the neck) and nerve palsies such as claw hand or foot drop.
Work-up of mononeuritis multiplex
- Nerve conduction studies and EMG: confirm several separate nerve lesions, mostly axonal.
- Blood: glucose/HbA1c, FBC, ESR/CRP, renal and liver function, ANCA, ANA, rheumatoid factor, complement, cryoglobulins, hepatitis B and C, HIV, protein electrophoresis.
- Urine: blood and protein (renal vasculitis), Bence Jones protein.
- Chest X-ray (sarcoid, malignancy, EGPA).
- Slit-skin smear or skin biopsy for leprosy.
- Nerve biopsy (usually sural), often with muscle biopsy, to prove vasculitis when blood tests do not settle it.
Treatment
- Treat the cause: glucose control in diabetes; corticosteroids plus cyclophosphamide or other immunosuppressants for systemic vasculitis; multidrug therapy for leprosy (and steroids for a leprosy reaction with nerve pain); antivirals for hepatitis-related disease.
- Physiotherapy, splints (foot drop, wrist drop) and pain relief for neuropathic pain.
Multifocal motor neuropathy with conduction block (MMN)
- Immune-mediated, purely motor, focal demyelinating neuropathy that develops over months, often asymmetric and in the hands.
- Shows wasting and fasciculation with no upper motor neurone signs, so it is easily mistaken for motor neurone disease.
- Nerve studies show conduction block; anti-GM1 ganglioside antibodies are found in over half of cases.
- Treatment: regular intravenous immunoglobulin. Steroids can make it worse and are avoided.
A patient with "MND" who has only lower motor neurone signs in one or two nerve territories and no bulbar involvement should have nerve studies looking for conduction block, because MMN is treatable.
A short word on polyneuropathy
Symmetrical sensorimotor polyneuropathy is covered with Guillain–Barré syndrome and B12 deficiency in other chapters. Common causes to remember: diabetes, alcohol, B12 and thiamine deficiency, uraemia, hypothyroidism, drugs (isoniazid, vincristine, metronidazole, phenytoin, nitrofurantoin, amiodarone), toxins (lead, organophosphates) and paraproteins. Isoniazid neuropathy is prevented by pyridoxine 10 mg daily. In about half of cases no cause is found despite investigation. Lead tends to cause a motor neuropathy with wrist drop.
Expect: the definition of mononeuritis multiplex and its causes (diabetes, vasculitis such as PAN, leprosy, RA, SLE, sarcoid, HIV); carpal tunnel syndrome associations (pregnancy, hypothyroidism, RA, acromegaly, dialysis amyloid), Tinel and Phalen tests, thenar sparing, nerve conduction for diagnosis and splint, injection or surgery for treatment; ulnar claw hand and Froment sign; Saturday night palsy with wrist drop; common peroneal palsy at the fibular neck with preserved inversion and ankle jerk versus an L5 root lesion; meralgia paraesthetica; demyelinating versus axonal changes on nerve studies; and multifocal motor neuropathy with conduction block as a treatable mimic of MND.
Quick revision
- Mononeuropathy = one nerve; mononeuritis multiplex = several separate nerves; polyneuropathy = symmetrical, distal.
- Demyelination: slow conduction. Axonal: low amplitude. Entrapment: focal demyelination.
- CTS: night tingling of radial 3½ fingers, thenar wasting, Tinel, Phalen; pregnancy, hypothyroid, RA, acromegaly, amyloid; splint → injection → release.
- Ulnar at elbow: claw hand, hypothenar and interossei wasting, little finger numb, Froment sign.
- Radial in spiral groove: wrist drop (Saturday night palsy).
- Common peroneal at fibular neck: foot drop, weak eversion, inversion and ankle jerk normal.
- Meralgia: outer thigh numbness, purely sensory.
- Mononeuritis multiplex: diabetes, vasculitis, leprosy, RA, SLE, sarcoid, HIV; sural nerve biopsy for vasculitis.
- MMN: motor only, conduction block, anti-GM1, IVIG, avoid steroids.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
What is the difference between mononeuritis multiplex and polyneuropathy?
Mononeuritis multiplex damages individual named nerves in a patchy, often asymmetrical pattern, while polyneuropathy affects all long nerves evenly, starting symmetrically in the feet.
Which blood test should every patient with carpal tunnel syndrome have?
Thyroid function and blood glucose are the usual first tests, because hypothyroidism and diabetes are common treatable associations.
Why is the ankle jerk normal in common peroneal palsy?
The ankle jerk depends on the tibial nerve and the S1 root, which are not involved when the common peroneal nerve is compressed at the fibular neck.
When is a nerve biopsy done?
Mainly when vasculitis is suspected in mononeuritis multiplex and blood tests are not conclusive; the sural nerve is usually chosen because it is purely sensory.