Mononeuritis Multiplex

Mononeuritis multiplex is the simultaneous or sequential involvement of two or more separate peripheral nerves, producing asymmetric, stepwise deficits that may merge into a symmetric polyneuropathy. It reflects multifocal nerve ischaemia, infiltration or inflammation.

Common causes: vasculitis (systemic or non-systemic), diabetes, leprosy, HIV, hepatitis B and C with cryoglobulinaemia, Lyme disease, sarcoidosis, amyloidosis, lymphoma and malignant infiltration, multifocal motor neuropathy, multifocal CIDP and hereditary neuropathy with pressure palsies.

Pathophysiology. Occlusion of vasa nervorum, immune attack or direct infiltration injures individual nerve trunks, especially in watershed zones.

Acute or subacute, often painful, sensory and motor loss in the distribution of individual nerves (peroneal, radial, ulnar, median), with new nerves added over days to months. Fever, weight loss, skin lesions, kidney, lung or gut involvement suggest systemic vasculitis.

Red flags.

• Acute wrist or foot drop with pain.
• Haematuria, haemoptysis, abdominal pain or rash.
• Rapid involvement of multiple nerves.

Nerve conduction studies show multifocal asymmetric axonal loss. Check full blood count, ESR, CRP, glucose and HbA1c, ANCA, antinuclear antibodies, complement, cryoglobulins, rheumatoid factor, hepatitis B and C, HIV, Lyme serology, angiotensin converting enzyme, urinalysis and chest imaging. Combined nerve and muscle biopsy is the key test for vasculitis. Skin biopsy in leprosy, and imaging or biopsy for lymphoma.

Differential diagnosis.

• Multiple compressive mononeuropathies and asymmetric diabetic neuropathy.
• Multifocal motor neuropathy, multifocal CIDP and motor neuron disease.
• Radiculopathies and plexopathies.

Treat the cause promptly.

Vasculitis. Methylprednisolone 1 g IV daily for 3 days, then prednisolone 1 mg/kg daily (maximum 60 mg) with a slow taper. For systemic or severe disease add cyclophosphamide 15 mg/kg IV every 2 to 3 weeks for 6 pulses, or rituximab 375 mg/m2 weekly for 4 weeks (or 1 g twice, 2 weeks apart). Maintenance with azathioprine 2 mg/kg daily or methotrexate 15 to 25 mg weekly, for 18 to 24 months.

Infection. Antibiotics for leprosy (multidrug regimen) or Lyme disease (doxycycline 100 mg twice daily for 14 to 21 days), and antiviral therapy for hepatitis B or C.

Diabetes. Optimise glycaemic control.

Other. Treat sarcoidosis, lymphoma or amyloidosis as the cause requires.

Supportive. Neuropathic pain (gabapentin, amitriptyline), splints, physiotherapy and foot care. Pneumocystis prophylaxis with co-trimoxazole during immunosuppression.

Monitoring. Neurological examination, inflammatory markers, renal and blood counts.

Referral and escalation. Refer urgently to neurology and rheumatology.