Statistics from Altmetric.com
New definitions will increase the significance of teased-fibre studies from both pathophysiological and diagnostic viewpoints
Although nerve biopsy is a classical approach, it still plays a role in the diagnosis and elucidation of the pathophysiology of neuropathy.1 There are two major techniques used to assess the morphology of nerve fibres in the longitudinal direction; one involves cutting glutaraldehyde-fixed epoxy-resin-embedded specimens into longitudinal sections and the other involves teasing the nerve fibres. Longitudinal sections are suitable for fine structural assessments using transmission electron microscopy to demonstrate, for example, paranodal pathology in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) displaying anti-neurofascin 155 antibodies.2 However, longitudinal sections are not useful for viewing complete pictures of long lesions that extend over several nodes of Ranvier.
Conversely, teased-fibre preparations enable observations of long nerve fibre sections. For example, the method of taking consecutive photographs of a single myelinated fibre from a patient with amyloid neuropathy revealed demyelination resulting from amyloid deposition at the proximal end of the fibre and dying-back axonal degeneration of the distal portion.3 The technique even showed subsequent sprouting of regenerating fibres from the proximal portion.3 These findings indicate that just one teased fibre can demonstrate the mechanisms of neuropathy. Moreover, teased-fibre preparations are useful in quantifying myelin and axonal lesions. From this standpoint, Dyck et al classified the morphology of teased fibres into nine types designated using alphabet letters A to I based on the condition of myelin and axons.1
In their JNNP paper, Min et al proposed an expansion to this classification of teased nerve fibres.4 They proposed new definitions and designated using alphabet letters J to M. These types of fibres were found in patients with CIDP, amyloid neuropathy, neurolymphomatosis and adult-onset polyglucosan body disease, respectively. An important aspect of these new definitions is that they represent specific mechanisms of neuropathy; type J fibres tend to result from demyelination over a long segment and an increase in surrounding interstitial tissues, type K and L fibres show amyloid deposits and cellular infiltrates around nerve fibres, respectively, and type M fibres represent focal axonal enlargement due to polyglucosan accumulation.
The conventional definitions of nerve fibre conditions (types A to I) are suitable for quantification of common lesions, such as demyelination, remyelination and axonal degeneration; however, the association of these findings with specific diseases is relatively weak.1 Nevertheless, these classifications have contributed to diagnoses, particularly to the identification of demyelinating neuropathies, such as CIDP. On the contrary, fibres compatible with the new definitions (types J to M) are relatively rare, but strongly associated with certain diseases.4 Therefore, the new definitions will improve the accuracy of diagnoses through nerve biopsy. The authors admit that there are some exceptions to the diseases that can be diagnosed using these definitions. Sensitivity and specificity of the new definitions should be clarified in future studies.
However, these new definitions will increase the significance of teased-fibre studies from both pathophysiological and diagnostic viewpoints. There may be fibres that still do not fall under any of the existing categories, for example, the condition of having n-hexane intoxication that causes marked swelling of axons accompanied by secondary demyelination. Future progress in the pathomorphology of neuropathy may elucidate additional novel definitions.
Contributors HK wrote the first draft and all authors critically evaluated the manuscript.
Funding This work was supported by grants from the Ministry of Health, Labor and Welfare (Research on Rare and Intractable Diseases, H29-022) and the Ministry of Education, Culture, Sports, Science and Technology (17K09777) of Japan.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Commissioned; internally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.