What causes marked motor mixed demyelinating and axonal changes with relative preservation of sensory conduction?

From the Guidelines

Marked motor mixed demyelinating and axonal changes with relative preservation of sensory conduction are typically caused by Guillain-Barré Syndrome (GBS), specifically the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype, as well as acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN) subtypes. These conditions are immune-mediated disorders characterized by rapidly progressive ascending weakness that initially affects the limbs and can eventually affect the cranial and respiratory muscles, with GBS being the most common cause of acute flaccid paralysis, with an annual global incidence of approximately 1–2 per 100,000 person-years 1. The pathophysiology involves an aberrant immune response to infections, which results in damage to peripheral nerves, with serum antibodies found against gangliosides in a subgroup of patients with GBS 1. The immune attack leads to demyelination and axonal degeneration of peripheral nerves and nerve roots, with electrophysiological studies providing evidence of PNS dysfunction and distinguishing between the subtypes of GBS 1.

Some key features of GBS include:

• Rapidly progressive ascending weakness
• Electrophysiological evidence of demyelination and axonal degeneration
• Relative preservation of sensory conduction
• Presence of serum antibodies against gangliosides in some patients
• Association with preceding infections, such as Campylobacter jejuni 1

Other conditions that can present similarly include multifocal motor neuropathy (MMN), Lewis-Sumner syndrome (MADSAM), motor neuron disease, and certain hereditary neuropathies, but the hallmark of GBS is the rapid progression of weakness and the presence of electrophysiological evidence of demyelination and axonal degeneration 1. Early diagnosis and treatment are essential to prevent irreversible axonal damage and permanent disability, with treatment options including immunomodulatory therapy, such as intravenous immunoglobulin (IVIG) and plasmapheresis 1.

It's worth noting that the evidence provided also mentions other conditions, such as dementia and Alzheimer's disease, but these are not relevant to the question of marked motor mixed demyelinating and axonal changes with relative preservation of sensory conduction 1. The most recent and highest quality study on this topic is the 2019 study on the diagnosis and management of Guillain-Barré Syndrome in ten steps, which provides a comprehensive overview of the condition and its treatment options 1.

From the Research

Causes of Marked Motor Mixed Demyelinating and Axonal Changes

• The causes of marked motor mixed demyelinating and axonal changes with relative preservation of sensory conduction can be attributed to various autoimmune disorders, including Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 2, 3, 4.
• These disorders are characterized by an aberrant immune response directed towards components of the peripheral nerve, causing demyelination and axonal damage 3.
• In some cases, the condition may be related to chronic motor axonal neuropathy (CMAN), a potentially treatable condition that is likely of immune-mediated origin 5.
• Additionally, axonal multifocal motor neuropathy without conduction block or other features of demyelination may also be a cause, although this is a rare condition 6.

Underlying Mechanisms

• The underlying mechanisms of these disorders involve an immune response that targets the peripheral nerve, leading to demyelination and axonal damage 3.
• The immune response may be mediated by cellular and humoral components, including antibodies and immune cells 3.
• In some cases, the condition may be triggered by an infection or other environmental factors, although the exact triggers are not fully understood 2.

Disease Characteristics

• GBS and CIDP are characterized by a rapid progression of symptoms, including weakness, paralysis, and sensory loss 2, 3, 4.
• CMAN is characterized by a rapidly progressive lower motor neuron syndrome associated with high titers of anti-GM1 antibodies 5.
• Axonal multifocal motor neuropathy is characterized by a slowly or nonprogressive multifocal motor neuropathy with purely axonal electrodiagnostic features 6.