MMNCB is rare, with an estimated prevalence of less than 1 in 100,000 people. It most commonly affects people born genetically male between 30 and 50 years old, with a male-to-female ratio of approximately 3:1. Due to its similarity to ALS and other motor neuron diseases, MMNCB is often underdiagnosed or misdiagnosed.

The exact cause of MMNCB is not fully understood but is thought to be autoimmune in nature. In the majority of patients with this rare disease, the antibody IgM is detected in blood samples. The immune system produces IgM antibodies against the GM1 ganglioside, a glycolipid component of motor neuron membranes. These antibodies disrupt nerve function by attacking the body’s healthy motor neurons and inducing demyelination (reducing the protective outer protein coating of the nerve cells). It can also cause conduction block, preventing a nerve’s signal from traveling all the way down the nerve to the desired muscle. This happens when IgM antibodies attack the nodes of Ranvier, which are gaps between myelin sheaths protecting the pathways of nerve cells, further disrupting the electrical signalling pathway. Unlike many other neuropathies, MMNCB typically affects only motor fibers, sparing sensory nerves.

MMNCB develops gradually and is characterized by:

• Asymmetric weakness of distal muscles, often beginning in the hands or forearms

• Difficulty bending or extending wrist or fine motor movements of the hands

• Cramps, fasciculations (brief contractions of the muscle right below the skin), or muscle twitching

• Absence of sensory loss, distinguishing MMNCB from most other peripheral neuropathies (should still be able to feel things with fingers, just not pick things up)

• Slow, progressive course, often spreading to other limbs over years

Weakness of muscles can cause severe fatigue in these areas and difficulty conducting physical activities. In advanced cases, weakness can cause significant disability, but respiratory (swallowing and breathing) and mental capabilities are rarely affected. Also unaffected are the touch sensations in the hands and feet. There is no feeling of numbness or tingling that is often associated with other neurodegenerative disorders in the extremities.

Diagnosis is based on the combination of clinical presentation, electrodiagnostic findings, and antibody testing. Because MMNCB mimics ALS and other motor neuron diseases, careful differentiation is essential. The hallmark finding is motor conduction block in nerve conduction studies, indicating impaired transmission along a motor nerve segment without evidence of axonal degeneration.

• Nerve conduction studies (NCS): Demonstrate conduction block in a specific localized area in motor nerves with normal sensory nerve conduction.

• Electromyography (EMG): Measurement of the electrical signals sent by neurons; May show reduced recruitment patterns consistent with lower motor neuron involvement but without denervation patterns typical of ALS.

• Anti-GM1 antibody test: Approximately 40–80% of patients have elevated IgM anti-GM1 antibodies.

• MRI of peripheral nerves or plexuses: Can show nerve enlargement or signal abnormalities due to inflammation.

• Cerebrospinal fluid (CSF) analysis: Usually normal or with mildly elevated protein; absence of inflammatory cells helps distinguish MMNCB from chronic inflammatory demyelinating polyneuropathy (CIDP).

The mainstay of treatment is intravenous immunoglobulin (IVIG) (or Gammagard Liquid ®), which can lead to significant improvement in muscle strength and slow disease progression. IVIG works by replacing unhealthy antibodies that are attacking neuron cells with healthy antibodies from a donor through an IV. However, only about 20% of patients with MMNCB that receive IVIG see their symptoms continue to improve, and most need continuous doses every 2-8 weeks for their lifetime.
Other treatment options include:

• Subcutaneous immunoglobulin (SCIG): For maintenance therapy in some patients.

• Immunosuppressive agents (e.g., cyclophosphamide, rituximab): Considered for refractory cases, although evidence is limited.

• Corticosteroids and plasma exchange: Generally ineffective and may worsen symptoms. Early initiation of therapy is crucial to prevent irreversible axonal damage and functional decline.

MMNCB is a chronic but treatable condition. With appropriate and ongoing treatment, most patients maintain independence and good quality of life. The disease course is slowly progressive, and while weakness can persist or recur between IVIG treatments, severe disability is uncommon. MMNCB does not typically affect life expectancy. However, delayed diagnosis or untreated disease can result in permanent muscle weakness due to axonal loss. Regular neurological follow-up and maintenance therapy are key to optimizing long-term outcomes.

1. Medscape: MMNCB

2. Cleveland Clinic: MMNCB

3. MMNCB: Autoimmune Association

4. https://www.ncbi.nlm.nih.gov/books/NBK554524/