Onion Bulb Formations: The Hallmark Histological Finding in CIDP
The hallmark histological finding in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) that indicates repetitive demyelination and remyelination is the presence of onion bulb formations. These structures represent the pathological evidence of cycles of demyelination and remyelination that occur in this chronic immune-mediated neuropathy 1.
Pathophysiology of Onion Bulb Formations
Onion bulb formations develop through the following process:
- During active disease, immune-mediated attacks target the myelin sheath surrounding peripheral nerve axons
- Schwann cells respond to demyelination by proliferating and attempting to remyelinate the affected nerve fibers
- With repeated cycles of demyelination and remyelination, Schwann cell processes become concentrically arranged around axons
- This creates the characteristic "onion bulb" appearance on histological examination, with concentric layers of Schwann cell processes surrounding a central axon
Diagnostic Significance
Onion bulb formations are particularly important in CIDP diagnosis for several reasons:
- They represent direct histological evidence of the chronic, recurring nature of the demyelinating process 2
- Their presence helps distinguish CIDP from acute demyelinating neuropathies where such formations have not had time to develop
- They can be found throughout the peripheral nervous system, including:
- Peripheral nerves
- Anterior and posterior spinal nerve roots
- Dorsal root ganglia
- Cranial nerves in longstanding cases 2
Clinical Correlation
The presence of onion bulb formations correlates with the clinical features of CIDP:
- The symmetrical, motor-predominant peripheral neuropathy seen in CIDP reflects the widespread demyelination
- Both proximal and distal weakness occurs as demyelination affects nerve segments throughout their length
- Large-fiber abnormalities (weakness and ataxia) predominate due to preferential involvement of large myelinated fibers 1
- The chronic progressive or relapsing-remitting course of CIDP allows time for these characteristic formations to develop
Limitations in Diagnostic Utility
While onion bulb formations are characteristic of CIDP, several caveats should be noted:
- They are not entirely specific to CIDP and can also be found in hereditary neuropathies, particularly hereditary motor and sensory neuropathy (HMSN) type I 3
- Sural nerve biopsies may show considerable overlap in findings between CIDP and chronic idiopathic axonal polyneuropathy (CIAP) 4
- The diagnostic value of sural nerve biopsy alone is limited, with one study showing no significant difference in the number of onion bulbs between CIDP and CIAP patients 4
Other Histopathological Features of CIDP
In addition to onion bulb formations, other histopathological findings in CIDP include:
- Segmental demyelination
- Endoneurial inflammatory infiltrates (primarily mononuclear cells)
- Variability in pathology between nerve fascicles
- Endoneurial edema (though not consistently present)
- Evidence of axonal degeneration in longstanding cases
Clinical Implications
Understanding the significance of onion bulb formations is important because:
- Their presence confirms the chronic nature of the demyelinating process
- They help distinguish CIDP from other neuropathies in challenging diagnostic cases
- In longstanding disease, their widespread distribution (including cranial nerves) explains the diverse clinical manifestations that can develop 2
- They represent the target pathology that immunomodulatory treatments aim to prevent by halting the cycles of demyelination and remyelination
The identification of onion bulb formations, along with other clinical and electrophysiological criteria, helps guide appropriate treatment with immunomodulatory therapies such as corticosteroids, plasma exchange, or intravenous immunoglobulin 1.