What is Multifocal Motor Neuropathy?
Multifocal motor neuropathy (MMN), also known as multifocal motor neuropathy with conduction block (MMNCB), is a rare, acquired disorder that affects the nerves controlling muscle movement. It leads to progressive weakness usually on one side of the body, without any sensory issues like numbness or tingling. This condition was first described in 1986 and more often affects the upper body than the lower body.
A special test called an electrodiagnostic study often shows an uneven impact on the nerves in different areas of the body, a feature termed as ‘conduction block’. Most patients have antibodies (proteins that usually fight infections) called anti-GM1 in their blood, which are thought to be involved in causing this disorder.
MMN is not considered a highly severe disorder with a poor outlook. In some cases, the symptoms are so mild that the patient may not need any treatment. However, in many cases, there could be a gradual increase in muscle weakness, especially in the hands and arms. This can make it challenging to perform simple daily activities like writing, washing, or dressing. On a positive note, these patients often show good response to a specific treatment known as intravenous immunoglobulin (IVIG), an infusion of antibodies that helps to modulate the body’s immune response.
What Causes Multifocal Motor Neuropathy?
Multifocal motor neuropathy is thought to be a type of nerve disorder caused by the immune system. This belief is supported by the high levels of a particular immune system protein, called IgM anti-GM1 antibodies, found in patients, and their favorable response to a treatment called intravenous immunoglobulin therapy (IVIG). The reason why this condition specifically affects motor nerves, which control muscle movement, more than sensory nerves, involved in feeling, is likely due to the fact that these motor nerves have more GM1, a type of substance towards which the antibodies are directed.
It was previously thought that this condition made nerve signals unable to pass through the nerves properly due to severe damage to the protective covering of the nerves, known as myelin. However, more recent evidence suggests that these anti-GM1 antibodies actually cause issues with the sodium and potassium channels at or around part of the nerve known as the node of Ranvier. These channels are crucial in carrying the nerve signals, thus contributing to the problems seen in multifocal motor neuropathy. This has led to the term ‘nodo-paranodopathy’ being used as well.
Additionally, a part of the immune system known as the complement system, which enhances (complements) the ability of antibodies and immune cells to clear microbes and damaged cells from an organism, seems to play a key role in the development of this disease.
Risk Factors and Frequency for Multifocal Motor Neuropathy
Multifocal motor neuropathy is a fairly uncommon health issue. Globally, less than 1 in 100,000 people are affected by it. Different parts of the world see varying rates – in Austria, the rate is 0.65 in 100,000 people, while in Japan, it’s 0.29 in 100,000. Men are more likely to be diagnosed than women, with it being around 2.7 times as common.
- Multifocal motor neuropathy is pretty rare, affecting less than 1 per 100,000 people worldwide.
- This rate can vary, such as in Austria where it’s 0.65 per 100,000 and in Japan where it’s 0.29 per 100,000.
- The disease is more frequently found in men, who are approximately 2.7 times as likely to have it compared to women.
- It is primarily diagnosed in adults between their thirties and fifties, though it can also be found in children as young as 6, and in elderly individuals.
Signs and Symptoms of Multifocal Motor Neuropathy
MMN, or Multifocal Motor Neuropathy, usually manifests as muscle weakness that slowly gets worse over time. The symptoms may start with things like a drooping wrist, finger weakness, or trouble lifting the foot, and can be worse on one side of the body. Even though the upper limbs (the arms and hands) are most commonly affected, the legs can also present weakness. Oddly enough, the cold weather might make these symptoms worse. Some patients might also feel pain or a tingling sensation, experience muscle cramps or twitching, or just feel unusually tired. It’s not common, but some patients could have issues involving the nerves in the head, face, and respiratory system.
Upon physical examination, doctors typically find that the muscles farthest from the body’s core (like hands and feet) are the weakest. The muscles affected usually depend on which nerves are involved. For example, if the radial nerve is compromised, the muscles controlling wrist and finger extension are more likely to be weak than the triceps muscle. It’s possible that some muscles are spared even if they are controlled by the same nerve bundle (called a myotome). So, if the median nerve is only partially affected, one thumb muscle could be weak while another thumb muscle is fine. Muscle shrinkage (atrophy) might occur, but usually, this is not severe given the extent of the weakness. Reflexes might be normal but could be decreased unevenly across the body. A key difference between MMN and a similar condition called ALS is that in MMN, there aren’t signs of damage to the upper motor neurons. Some patients with MMN may also have muscle spasms.
Testing for Multifocal Motor Neuropathy
In a condition called multifocal motor neuropathy, electrical tests can help track how well your nerves are working. If you have this issue, your motor nerves–the nerves that control muscle movement–may not function properly, while your sensory nerves–the ones that handle feeling–might be fine. In some cases, the motor nerves may work more slowly than they should. We usually see this issue occur higher up in the nerve, making it harder to test and diagnose with routine methods.
In this condition, when there’s a more than 50% decrease in the strength of the muscle’s response between two points along a nerve, it could signal a problem. This typically occurs in non-compressible sites—places where the nerves can’t be easily pinched or compressed. However, this kind of conduction block can also occur in other conditions like chronic inflammatory demyelinating polyneuropathy (CIDP), and Guillain-Barre syndrome (GBS).
Standard blood and urine testing usually doesn’t show anything unusual if you have multifocal motor neuropathy. Tests that look at your cerebrospinal fluid (the fluid that surrounds your brain and spinal cord) can help distinguish this condition from others like CIDP.
In about half the people with this condition, we can find antibodies (proteins your body usually makes to fight off infections) called Anti-GM1. Testing for GM1/galactocerebroside (GM1/GalC) complexes can improve the chances of finding these antibodies.
Imaging techniques like ultrasound and MRI can provide additional information for diagnosis, especially when other tests are not giving definitive answers. An MRI might show abnormal signals in the brachial plexus, a group of nerves that runs from your neck to your arm. If these signals are one-sided, it could be a sign of this condition. Ultrasound might show a larger-than-normal median and ulnar nerve—the main nerves running down your arm.
The European Federation of Neurological Societies (EFNS) and Peripheral Nerve Society (PNS) Task Force have come up with a set of criteria to assist in making a diagnosis:
– You must have progressive, asymmetric weakness in at least two nerve areas that lasts for at least a month.
– You can’t have any significant sensory problems except for possible minor issues with feeling vibrations in your lower legs.
– Other supportive signs include mostly upper body involvement, decreased reflexes in the affected limb, no cranial nerve issues, muscle spasms and twitching in the affected limb, and improvement from immunomodulatory treatments—treatments that help regulate your immune system.
– The criteria also include symptoms that, if present, would exclude this condition, such as issues with upper motor neurons, significant bulbar involvement, more pronounced sensory problems in the lower legs, or uniformly weak muscles when the symptoms first start.
Treatment Options for Multifocal Motor Neuropathy
For a condition known as MMNCB, the primary medical treatment option is a medicine delivered through an IV, called IVIg. It’s worth noting that this treatment works well for many patients, with more than three-quarters seeing positive results. However, these improvements in muscle strength tend to be short-term and only about 20% of patients experience long-term improvements. Because of this, most patients need to continue to receive IVIg treatments periodically. Even with regular treatments, some patients may experience slow progress in motor skill deficits, which may be due to secondary damage to the nerve fiber (axon).
A summary of several studies (known as a Cochrane review) concluded that IVIg was more effective than a placebo for treating MMNCB. It’s typically first given at a certain rate for five days, and then the dose is adjusted based on the patient’s condition. Since Ig is generally given for long durations, sometimes even years, a method of administering this medicine under the skin, known as SCIG, has been tested. As per clinical investigations, SCIG seems to be safe, equally effective, feasible, and can be self-administered at home.
For patients who don’t respond to IVIg, the treatment options are more limited. Alternatives such as immunomodulatory agents or medicines that help regulate the immune system, including cyclophosphamide, mycophenolate mofetil, azathioprine, and rituximab, have been studied with mixed results. For example, oral cyclophosphamide has been reported to be effective in maintaining disease remission and reducing the frequency of IVIg treatments, but it has significant side effects. There is still a need for more comparative studies to establish the effectiveness of these immunomodulatory drugs in MMN.
Lastly, while all these methods are used, there are treatments for MMN that seem not to be effective, such as corticosteroids and plasmapheresis (a procedure that filters the blood to remove harmful substances).
What else can Multifocal Motor Neuropathy be?
There are several conditions that could be mistaken for multifocal motor neuropathy. These include ALS, CIDP, and hereditary neuropathy with liability to pressure palsies (HNPP). Other possibilities could be radiculopathy, nerve entrapment syndromes, mononeuritis multiplex, hereditary motor neuropathies, porphyria, and lead intoxication. It’s important to understand the differences between these conditions, as their symptoms can often be similar.
- Amyotrophic Lateral Sclerosis (ALS) and multifocal motor neuropathy both present with progressive pure motor weakness. However, ALS typically progresses faster than multifocal motor neuropathy. ALS also often affects the entire muscle group at once, causing noticeable muscle atrophy and twitching. Meanwhile, multifocal motor neuropathy typically results in less pronounced muscle atrophy, particularly early in the disease.
- Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) can cause muscle weakness and reduced deep tendon reflexes over time. However, the muscle weakness in CIDP is often symmetrical and it affects legs more than arms. Unlike multifocal motor neuropathy, CIDP common involves the sensory nerves. There are also purely motor variants of CIDP which can make it hard to differentiate from multifocal motor neuropathy.
- Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) presents with asymmetric motor weakness in the distribution of multiple motor nerves. However, it’s distinguished by the fact that the conduction blocks typically occur at known nerve entrapment sites. Also, sensory symptoms are prominent in HNPP, and patients often have a positive family history of the disease since it’s inherited.
Understanding these differences is crucial because treatment response for each of these conditions can vary. The goal is to arrive at an accurate diagnosis, and then implement the most effective treatment plan.
What to expect with Multifocal Motor Neuropathy
The outlook for people with multifocal motor neuropathy is generally positive. Around 80% of patients see improvements with a treatment known as IVIG, which stands for intravenous immunoglobulin. This treatment involves delivering antibodies to the patient through a vein. Roughly a fifth of patients experience long-term improvements, while others continue to need regular IVIG treatments or a similar treatment called SCIG, which is short for subcutaneous immunoglobulin and is administered under the skin.
Even among patients who don’t respond to these treatments, the muscle weakness associated with the condition usually progresses at a slow pace. Most patients can still carry out their daily activities. In a certain study, it was found that more than 94% of the patients remained employed.
In 2015, a group of researchers validated a tool called the Rasch-built Overall Disability Scale for MMN. This is a 25-item checklist that helps doctors track the progression of the disease and how well the treatment is working.
Possible Complications When Diagnosed with Multifocal Motor Neuropathy
Multifocal motor neuropathy usually isn’t deadly because it doesn’t affect the muscles controlling breathing or those in the head. Most issues arise from the treatments.
These treatment complications may include:
- IVIG, a type of treatment, could lead to blood clots (that might result in heart attacks, strokes, or blood clots in large veins), kidney failure, severe allergic reactions, non-infectious inflammation of brain membranes, and in rare cases, lung injury related to the transfusion.
- Cyclophosphamide, another treatment, might lead to decreased blood cell production, bleeding and inflammation in the bladder, and inflammation in the lung tissue.
Preventing Multifocal Motor Neuropathy
Currently, we don’t know of any reliable methods to prevent this condition. However, it’s crucial for patients to understand the nature of the disease and its usual progression. In most cases, patients will need sustained treatments with Intravenous Immunoglobulin (IVIg) and Subcutaneous Immunoglobulin (SCIg). These are medicine given into your veins or under your skin to improve immune system function. Be aware, though, they can be expensive and might come with unwanted side effects. Despite ongoing treatment, the disease might continue to worsen, but the good news is it’s usually not life-threatening.
The condition often affects the muscles in the hands, which could make writing and other specialized hand movements challenging. So, discussing and thinking about other job possibilities may be necessary.
