Hereditary Neuropathy with Liability to Pressure Palsies

Hereditary neuropathy with liability to pressure palsies is an autosomal dominant inherited neuropathy characterised by recurrent, painless focal nerve palsies after minor compression or stretch. It is caused by a deletion of PMP22 on chromosome 17.

The prevalence is about 2 to 16 in every 100,000 people, and it is under diagnosed. Onset is usually in the second to third decade, and men and women are equally affected.

Genetics. The commonest cause is a 1.5 megabase deletion containing PMP22 (the reciprocal of the duplication that causes CMT1A), and point mutations in PMP22 are rarer.

Course. Individual palsies usually recover over days to months, but recovery can be incomplete and a mild generalised neuropathy may develop over time. Some patients are asymptomatic.

Pathophysiology.

Reduced PMP22 dosage leads to abnormal myelin with focal thickening (tomacula), making nerves vulnerable to compression and stretch.

Conduction block follows mechanical stress at common entrapment sites.

• Painless recurrent mononeuropathies after trivial compression: peroneal palsy (foot drop) after leg crossing or kneeling, ulnar palsy after leaning on the elbow, carpal tunnel syndrome, radial palsy after sleep.
• Brachial plexopathy in some, after stretch.
• Mild distal sensory loss, reduced reflexes, pes cavus and wasting in a minority.
• A history of recurrent palsies, often in a relative.

Red flags.

• Severe, painful or progressive palsy (nerve trauma, vasculitis, inflammatory neuropathy).
• Palsies in patients with no family history, with systemic features or elevated inflammatory markers.
• Palsy after surgery or prolonged immobilisation (compression injury).

• Nerve conduction studies show a generalised, mild slowing of conduction with focal slowing or block at common entrapment sites (carpal tunnel, ulnar groove, fibular head), even in unaffected nerves.
• Genetic testing for the PMP22 deletion is diagnostic.
• MRI or ultrasound of the affected nerve to exclude a structural cause; blood tests to exclude diabetes, thyroid disease and vasculitis.
• Family history and examination of relatives.

Differential diagnosis. Charcot-Marie-Tooth disease type 1A, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, vasculitic neuropathy, diabetic mononeuropathy, traumatic nerve injury and entrapment neuropathy.

• Prevention is the mainstay: avoid prolonged leg crossing, kneeling and squatting, leaning on the elbows, repetitive wrist movements, heavy straps and tight cuffs; use padding and ergonomic aids.
• Wrist splints at night for carpal tunnel symptoms; elbow pads for ulnar nerve protection.
• Ankle foot orthosis for foot drop during recovery; physiotherapy to maintain range of movement.
• Most palsies recover spontaneously; surgical decompression is not usually needed and is considered only for persistent focal compression.
• Avoid neurotoxic drugs such as vincristine, which can cause severe neuropathy; review other drugs with a neurotoxic effect before use.
• Careful positioning during surgery and anaesthesia, with documented warnings.
• Genetic counselling for family members.
• Painful episodes: paracetamol 1 g orally every 6 hours as needed, maximum 4 g in 24 hours (3 g if under 50 kg, chronic alcohol excess or liver disease), for the shortest period that controls pain. Monitor liver function with prolonged use. Reduce dose in hepatic impairment; extend the interval when eGFR is under 30.

Monitoring. Review at 3 to 6 months after a palsy, then yearly; repeat nerve conduction studies when function changes.

Referral and escalation. Neurology or neuromuscular specialist for diagnosis; genetics for counselling; orthopaedics or neurosurgery for persistent compression.

Special groups. Pregnancy and surgery: protect pressure points. Children: school and sports advice, avoiding prolonged compression.