From the Guidelines
Diffuse peripheral axonal loss is most commonly caused by vitamin B12 deficiency, as evidenced by a study published in 2018 1, which highlights the significant negative impact of vitamin B12 deficiency on nerve conduction velocity and the association with extensive demyelination and axonal degeneration in the peripheral nervous system. The causes of diffuse peripheral axonal loss can be multifactorial, including:
- Vitamin deficiencies, particularly B12, as noted in the 2018 study 1, which emphasizes the importance of adequate vitamin B12 intake to prevent neuromuscular dysfunction
- Autoimmune disorders, such as Guillain-Barré syndrome, which is discussed in a 2019 study 1 that provides a comprehensive guideline for the diagnosis and management of the condition
- Infectious diseases, such as HIV, Lyme disease, and leprosy
- Hereditary conditions, like Charcot-Marie-Tooth disease
- Metabolic disorders, including hypothyroidism
- Toxin exposure, including heavy metals and industrial chemicals
- Certain systemic diseases, such as kidney or liver failure, and paraneoplastic syndromes associated with cancer The pathophysiology of diffuse peripheral axonal loss typically involves damage to the axons themselves, often through mechanisms of oxidative stress, mitochondrial dysfunction, or direct toxic effects, as discussed in the context of vitamin B12 deficiency 1 and Guillain-Barré syndrome 1. Symptoms of diffuse peripheral axonal loss can include numbness, tingling, weakness, and pain, typically beginning in the distal extremities and progressing proximally in a "stocking-glove" distribution, highlighting the importance of early identification and management of the underlying cause to prevent further nerve damage.
From the Research
Causes of Diffuse Peripheral Axonal Loss
- The causes of diffuse peripheral axonal loss can be attributed to various factors, including:
- Genetic defects, which can lead to inherited peripheral neuropathies 2
- Acquired factors, such as toxins, mechanical injuries, metabolic disorders, nutritional deficiencies, inflammation, and infections 2, 3
- Vitamin and mineral deficiencies, which can cause peripheral neuropathy 3
- Prescription medications, which can also lead to peripheral neuropathy 3
- Traumatic brain injury, which can result in diffuse axonal injury (DAI) 4, 5
- The length-dependent nature of peripheral neuropathies suggests an important role for disturbances in axonal transport, which can be directly or indirectly linked to alterations in the cytoskeleton 2
- Axon degeneration is a key mechanism in the development of peripheral neuropathy, and recent studies have identified SARM1 as an injury-activated NADase enzyme that triggers axon degeneration 6
- Inhibiting the SARM1 pathway may provide a therapeutic opportunity for the prevention and treatment of peripheral neuropathy 6