Are there any brain MRI changes in Charcot-Marie-Tooth (CMT) disease?

Brain MRI Changes in Charcot-Marie-Tooth Disease

Brain MRI abnormalities can occur in CMT, particularly in X-linked CMT (CMTX1), though the brain is typically normal in most CMT subtypes affecting only peripheral nerves.

Key MRI Findings in CMTX1

CMTX1, caused by GJB1 gene mutations, is the primary CMT subtype associated with central nervous system involvement:

Acute/Subacute Presentations

• White matter lesions resembling ADEM can occur, appearing as demyelinating lesions in the centrum semiovale and cerebral white matter that may completely resolve on follow-up imaging 1, 2
• These stroke-like or transient ischemic attack-like episodes represent a rare but recognized manifestation of CMTX1 1, 2
• Recurrent demyelinating lesions may develop years after initial presentation, sometimes accompanied by dysarthria 2

Chronic Structural Changes (in asymptomatic CMTX patients)

Advanced neuroimaging reveals multiple abnormalities even without current CNS symptoms 3:

Gray matter changes:

• Decreased gray matter density in bilateral hippocampus, left thalamus, left postcentral gyrus, left superior parietal lobule, left cerebellum (crus I and II), and vermis VI 3

White matter changes:

• Increased fractional anisotropy and radial diffusivity in right anterior insula 3
• Increased axial diffusivity in right cerebellum crus I 3

Functional changes:

• Decreased spontaneous neural activity in left precentral gyrus on resting-state functional MRI 3

Cranial Nerve Involvement

MRI may demonstrate:

• Smoothly enlarged, mildly enhancing trigeminal nerves 4
• Smooth, symmetric enlargement and mild enhancement of facial nerves 4
• Associated bony widening of skull base foramina on CT 4
• These findings typically occur without corresponding clinical symptoms 4

Spinal Imaging Findings

While not brain-specific, spinal MRI shows:

• Smooth, symmetric enlargement and mild enhancement of distal spinal nerve roots and cauda equina 4

Central Conduction Abnormalities

Electrophysiologic studies reveal CNS impairment in CMT1A:

• Significantly prolonged central conduction time (7.05 ± 2.09 ms vs 5.40 ± 1.79 ms in controls) 5
• Six of 30 CMT1A patients showed abnormal brain MRI signals, though these did not correlate with conduction abnormalities 5

Clinical Implications

The presence of brain MRI abnormalities should prompt consideration of CMTX1, particularly when:

• Recurrent neurological episodes occur with ADEM-like imaging 2
• Stroke-like symptoms develop in young patients with peripheral neuropathy 1
• Physical examination reveals pes cavus deformities and peripheral muscle wasting alongside CNS symptoms 2

Genetic testing for GJB1 mutations is essential when brain involvement is suspected, as this confirms CMTX1 diagnosis and has implications for genetic counseling 1, 2

Diagnostic Pitfalls

• Do not dismiss the possibility of CMT when white matter lesions suggest ADEM, especially if peripheral neuropathy signs are present 2
• Cranial nerve enlargement on MRI does not necessarily correlate with clinical symptoms and should not be used as the sole diagnostic criterion 4
• Normal brain MRI does not exclude CNS involvement, as functional and microstructural changes may precede visible abnormalities 3, 5
• Most CMT subtypes (particularly CMT1A, CMT2, and others) typically do not show brain MRI abnormalities, making CMTX1 the primary consideration when central findings are present 1, 3, 2