Neuralgic Amyotrophy

Neuralgic amyotrophy (Parsonage-Turner syndrome, idiopathic brachial plexus neuritis) is a multifocal, immune-mediated inflammatory neuropathy of the brachial plexus and its branches. It is characterised by severe pain followed by patchy weakness and wasting.

• Reported incidence is 1 to 3 per 100,000 per year, but true incidence is probably nearer 1 per 1,000 because mild cases are missed.
• Men are affected up to 2 to 4 times more often than women. Peak onset is the third to seventh decade.

Triggers are identified in about half of cases

• Preceding infection, mostly viral (upper respiratory, influenza, COVID-19), and hepatitis E.
• Vaccination, surgery, strenuous exercise, trauma, childbirth and the postpartum period.
• Autoimmune disease and immune checkpoint inhibitor therapy.

A hereditary form (hereditary neuralgic amyotrophy) has autosomal dominant inheritance with SEPT9 mutations. It begins earlier, relapses frequently, and may show hypotelorism, cleft palate, and facial skin folds.

Pathophysiology

• A T-cell and antibody mediated inflammatory attack, likely in a genetically or mechanically predisposed host, damages individual fascicles.
• Imaging and surgical series show focal hourglass-like constrictions of affected nerves, with torsion of fascicles.
• Axonal loss predominates, so recovery depends on regeneration.

Nerves most affected are the suprascapular, long thoracic, axillary, musculocutaneous, anterior interosseous, posterior interosseous and the upper trunk. The phrenic nerve is involved in 5 to 10%, the recurrent laryngeal nerve occasionally, and a lumbosacral variant exists.

Prognosis

• About one third recover by 1 year, 75% by 2 years, and 90% by 3 years.
• Persistent pain, scapular instability and weakness are common.
• Recurrence occurs in about 25%, and much more often in the hereditary form.

The syndrome has two phases

• Painful phase: abrupt severe pain in the shoulder, scapular region, neck or upper arm, described as sharp, stabbing or burning. It is worst at night, unrelieved by position and unrelated to neck movement. It lasts days to weeks, with an average of 4 weeks.
• Paralytic phase: weakness appears as pain subsides, usually within days and up to 2 weeks after onset, followed by atrophy.

Typical weakness patterns

• Shoulder girdle: supraspinatus and infraspinatus (weak abduction and external rotation), deltoid, and serratus anterior with scapular winging.
• Arm: biceps weakness, and radial nerve branch involvement.
• Forearm: anterior interosseous palsy (failed OK sign, weak pinch, weak pronator quadratus) and posterior interosseous palsy (finger drop).
• Phrenic involvement: dyspnoea, orthopnoea, and a raised hemidiaphragm.
• Recurrent laryngeal involvement: hoarseness.

Other findings

• Sensory loss is usually mild and patchy, and is out of proportion to the weakness.
• Bilateral but asymmetric disease occurs in 10 to 30%.
• Reflexes are reduced in the affected territory. Cervical spine movement is normal.

Differential diagnosis includes

• Cervical radiculopathy, rotator cuff tear, adhesive capsulitis.
• Pancoast tumour, neoplastic and radiation plexopathy, thoracic outlet syndrome.
• Guillain-Barré syndrome, CIDP and multifocal motor neuropathy.
• Motor neuron disease, spinal cord lesions, herpes zoster, and hereditary neuropathy with liability to pressure palsies.

Features arguing against the diagnosis are neck-movement-provoked pain, a persisting sensory level, and progressive weakness beyond 2 months.

Diagnosis rests on the characteristic history of acute severe pain followed by weakness in a plexus or multi-nerve distribution.

Electrodiagnostic testing

• Needle EMG at 3 weeks or more shows denervation (fibrillations, positive sharp waves) in muscles from multiple nerves and roots, with sparing of the cervical paraspinals. Sparing of the paraspinals separates neuralgic amyotrophy from radiculopathy.
• Nerve conduction studies show reduced CMAP and sensory amplitudes (lateral antebrachial cutaneous, radial) with normal velocities.
• Early studies at under 2 to 3 weeks can be normal.

Imaging

• MRI of the cervical spine and brachial plexus excludes structural, neoplastic and compressive causes.
• T2 hyperintensity of affected muscles (denervation oedema) appears within days, and the nerve itself may be swollen and hyperintense.
• High resolution ultrasound or MR neurography detects focal constrictions, useful for selecting surgical candidates.
• Chest radiograph, diaphragm ultrasound or sniff test for suspected phrenic palsy.

Laboratory evaluation

• ESR, CRP, HbA1c, vitamin B12, and Lyme serology in endemic areas.
• Hepatitis E RNA and IgM, HIV, and rheumatological screens as indicated.
• CSF is typically normal or shows modestly raised protein, and is reserved for atypical presentations.
• SEPT9 sequencing in recurrent or familial cases.

Pain control

• Paracetamol 1 g up to four times daily and NSAIDs (naproxen 500 mg twice daily) are often inadequate alone.
• Neuropathic agents: gabapentin 300 mg at night titrated to 600 to 1200 mg three times daily, pregabalin 75 mg twice daily increased to 150 to 300 mg twice daily, amitriptyline 10 to 75 mg at night, or duloxetine 60 mg daily.
• Short-term opioids (tramadol 50 mg every 6 hours, or oxycodone 5 mg every 4 to 6 hours) for the severe early phase.
• A sling for comfort, used briefly.

Immunotherapy

• Early oral corticosteroids, started within 2 to 4 weeks of onset, shorten the pain phase and may improve recovery: prednisolone 60 mg daily for 5 to 7 days, then tapered over 2 to 3 weeks.
• Methylprednisolone 1 g IV daily for 3 to 5 days is used for severe pain, followed by an oral taper.
• IVIG 2 g/kg divided over 2 to 5 days for persistent, relapsing or hereditary disease.
• Hepatitis E associated cases with immunosuppression or chronic infection are managed with hepatology input and ribavirin where indicated.

Rehabilitation

• Passive and active assisted range of motion from the early phase to prevent adhesive capsulitis.
• Scapular stabilisation and strengthening once pain settles. Avoid heavy resistance in the first weeks.
• Occupational therapy, shoulder support, and taping of the winged scapula.
• Ventilatory monitoring in bilateral phrenic palsy, with non-invasive ventilation when needed.

Surgery

• Imaging-confirmed hourglass constrictions of the anterior or posterior interosseous nerve, or other nerves, with no clinical recovery by about 6 months: interfascicular neurolysis or nerve grafting, with good reported outcomes.
• Nerve transfers or tendon transfers for persistent deficits beyond 12 to 18 months.
• Scapulothoracic fusion or static stabilisation for persistent winging.
• Diaphragmatic plication for symptomatic persistent phrenic palsy.

Counselling and follow-up

• Explain the self-limiting course, the 2 to 3 year recovery horizon, and recurrence risk.
• Advise patients of the hereditary form on genetic counselling and avoidance of triggers such as heavy exertion during relapse risk periods.
• Review at 3, 6 and 12 months with serial EMG if recovery stalls.