Multifocal motor neuropathy: symptoms, diagnosis and immunoglobulin treatment

The Walton Centre, a specialist neuroscience NHS trust, breaks the name down: multifocal means affecting more than one area, motor means the nerves affected are those that carry signals from the brain and spinal cord to the muscles, and neuropathy means disease of the nerves. The damage involves the nerves in the arms and legs, which are part of the peripheral nervous system.

The problem lies with the immune system acting against the coating of the peripheral nerves. The Walton Centre says it is not known exactly why this happens, and that the condition is neither inherited from your parents nor spread from one person to another. The nerve damage interferes with signals going from the brain to the muscles, which causes weakness in the limbs, most commonly in the hands.

A review for clinicians in Mayo Clinic Proceedings, a US journal, describes MMN as rare, with a prevalence of less than 1 in 100,000, and says it affects men more commonly than women, at a ratio of about 3 to 1, usually starting in the fourth or fifth decade of life.

The Mayo Clinic Proceedings review says weakness first develops in the upper limbs in about 80 per cent of patients and tends to affect the distal muscles, those of the hand and forearm. About 20 per cent of patients first notice weakness in the legs. The weakness is typically focal and asymmetric, following the distribution of individual named nerves, and it comes without pain or significant sensory loss. Cramps and twitching (fasciculations) may occur in up to 40 per cent of people.

Some people progress slowly, while others have stepwise or abrupt deteriorations as new motor nerves become involved. Because of the focus on the hands, most people develop restrictions in fine motor skills such as household, work and leisure activities, and weakness in the lower legs can limit walking.

The Walton Centre emphasises that not everyone is affected in the same way: some people have only minor symptoms while others have severely disabling symptoms, and most fall between these extremes. Some have fluctuating symptoms but most have progressive disease which responds to treatment.

Diagnosis is usually made by a neurologist with an interest in neuromuscular disease. The pattern of weakness, the absence of pain and sensory findings, and nerve conduction studies are the central elements. The Mayo review says the key distinguishing finding is conduction block at noncompressible sites, meaning the electrical signal is interrupted along a stretch of nerve where it is not simply being squeezed by a normal anatomical narrowing.

Where the conduction block is not clear, the review says blood tests for anti-GM1 IgM antibodies, which are detected in at least 40 per cent of people with MMN, thickened nerves on MRI or ultrasound, or a response to intravenous immunoglobulin can support the diagnosis.

Recognition matters because other conditions look similar. The review lists motor neurone disease (ALS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), inclusion body myositis, hereditary neuropathy with liability to pressure palsy, focal neuropathies and radiculopathies. It notes that diagnostic delay of more than a year is common. It also warns that, unlike CIDP, people with MMN may paradoxically worsen when given corticosteroids or plasma exchange, which is one reason an accurate diagnosis changes treatment.

The Walton Centre says treatment focuses on interfering with the immune attack, and that physiotherapy and occupational therapy are also important parts of care for many people. The only effective treatment it names is immunoglobulin therapy, given by a vein initially, with some people able to move to treatment under the skin. Doses are tailored to each person and discussed before prescribing. The treatment works by suppressing the immune system's activity against the nerves, which reduces nerve inflammation and damage.

It is open about what treatment can and cannot do. It does not cure MMN; it usually suppresses disease activity, leading to improvement and sometimes resolution of symptoms, but regular treatment is usually required, sometimes lifelong. Response varies widely, and most people with weakness improve significantly, but not everyone does, especially if weakness has been present a long time and is associated with muscle wasting. Without treatment, the Walton Centre says, the nerve damage usually progresses.

On repair, it says the fatty coating around the nerve can regenerate over weeks to months once inflammation settles, but longstanding damage with muscle wasting does not usually improve greatly. The Mayo review similarly stresses that accumulating axon loss, which is worsened by delayed treatment, is the main predictor of irreversible disability.

Practical issues revolve around hand function: dressing, writing, cooking and work tasks. Occupational therapy can suggest adaptations and techniques, and physiotherapy works on the strength and function of the muscles. The Walton Centre notes that treatment is supervised and monitored for side effects, and that the small associated risks are discussed before treatment starts.

The Mayo review recognises a psychological burden as well as a physical one, particularly after a long period of uncertainty and misdiagnosis. Being told you do not have motor neurone disease, and that your life expectancy is normal, can be a relief, but living with a lifelong condition that needs regular infusions is demanding in its own right.

Because MMN is rare, diagnosis and treatment are usually led by neuromuscular specialists in neurology centres, and immunoglobulin is given under supervision. The Mayo review encourages referral to a centre with expertise in rare inflammatory neuropathies, and the Walton Centre, a specialist NHS neuroscience trust, is one example of such a service.

Some people seek a private neurology opinion, mostly to speed up the first assessment and nerve conduction studies, or to get a second opinion about a possible diagnosis of motor neurone disease. Long-term immunoglobulin treatment is generally delivered through specialist NHS centres, so it is worth asking early how any private assessment will connect to NHS treatment.