What is acquired hypertrophic neuropathy?

Acquired Hypertrophic Neuropathy

Acquired hypertrophic neuropathy is a rare peripheral nerve disorder characterized by pathological nerve enlargement due to chronic demyelination and remyelination, most commonly caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), presenting with progressive weakness, sensory loss, and radiating pain. 1, 2

Pathophysiology and Pathological Features

• The hallmark pathological finding is "onion bulb" formation, which represents concentric layers of Schwann cell processes surrounding demyelinated axons, visible on S-100 immunostaining 2
• Two primary pathological patterns exist: degenerative neuropathy (with neuronal swelling, intranuclear inclusions, axonal degeneration, and hypoganglionosis) or inflammatory neuropathy (with lymphocytic or eosinophilic plexitis and neuritis) 3
• The condition results from repeated cycles of demyelination and remyelination, causing progressive nerve thickening that can reach up to 10-fold normal nerve diameter 4

Clinical Presentation

• Onset and progression: Insidious onset in adulthood or old age, with slowly progressive symptoms over months to years 3, 1
• Motor symptoms: Progressive bilateral lower-extremity weakness, gait ataxia, and hyporeflexia 2, 4
• Sensory symptoms: Radicular pain (particularly in buttocks and thighs), sensory loss in lower extremities, and paresthesias 1, 2
• Distinctive feature: Significant discrepancy between severe nerve hypertrophy on imaging and relatively mild clinical symptoms 4

Diagnostic Evaluation

Electrophysiological Studies

• Markedly slow nerve conduction velocities (inversely correlated with degree of nerve enlargement) 4
• Multiple conduction blocks and absence of F-waves 4
• Increased distal compound muscle action potential (CMAP) duration 4

Cerebrospinal Fluid Analysis

• Markedly elevated protein levels without pleocytosis 4

Imaging Findings

• MR neurography: Diffuse nerve swelling with significant variability within different segments of the same nerve, showing enlargement outside typical entrapment sites 4, 5, 6
• Spinal MRI: Hypertrophy of spinal roots and cauda equina with gadolinium enhancement, appearing as multiple poorly enhancing intrathecal mass lesions 2, 4
• Brain MRI: Hypertrophic cranial nerves with gadolinium enhancement 4
• MRI serves as a supplementary diagnostic tool to guide fascicular biopsy location 6

Pathological Confirmation

• Nerve biopsy demonstrating extensive "onion bulb" formation with S-100 positivity confirms the diagnosis 2
• Biopsy should be performed on segments identified as enlarged on MR neurography 6

Differential Diagnosis

The primary differential diagnoses for acquired hypertrophic neuropathy include:

• Hereditary motor and sensory neuropathy (HMSN): Distinguished by family history and genetic testing 6
• Neurofibromatosis type 1: Identified by characteristic cutaneous findings and genetic testing 6
• Intraneural perineurioma: Requires histopathological differentiation 6
• Mitochondrial disorders: Can present with polyneuropathy (96% in MNGIE) but accompanied by multisystem manifestations including leukoencephalopathy, ophthalmoplegia, and gastrointestinal dysmotility 3

Treatment Approach

Medical Management

• First-line therapy: Intravenous immunoglobulin (IVIG) for CIDP-related hypertrophic neuropathy, which typically produces symptomatic improvement in relapsing-remitting disease 1, 4
• Long-term maintenance: Oral corticosteroid therapy following initial immunoglobulin treatment 1
• Medical management alone has limited effect on compressive symptoms caused by intradural nerve root enlargement 2

Surgical Management

• Indication: Symptomatic radiculopathy with compressive symptoms unresponsive to medical therapy 2
• Procedure: Decompressive lumbar laminectomy with dural expansion using a dural patch (typically 11 cm or longer) 2
• Intraoperative monitoring: Continuous somatosensory evoked potential and electromyographic monitoring to identify non-functional nerve roots 2
• Combined approach: Spinal canal decompression combined with specific etiological interventions (immunotherapy) produces optimal outcomes, even in pediatric patients 1

Postoperative Rehabilitation

• Structured rehabilitation training improves lower-limb muscle strength and functional mobility 1
• Progressive improvement typically occurs over 6-12 months post-surgery when combined with immunotherapy 1

Prognosis and Clinical Course

• The condition typically follows a relapsing-remitting course with response to immunotherapy 4
• Nerve enlargement correlates directly with disease duration and inversely with nerve conduction velocity, but does not correlate with disease severity 4
• Surgical decompression combined with immunotherapy can restore normal ambulation within one year in appropriately selected patients 1
• Associated with high morbidity, though this is usually due to factors other than the neuropathy itself 3