Changes in Sciatic Nerve of Thigh May Reflect Disability in CMT1a Patients

The myelin sheath is a fat-rich substance that covers nerve fibers and allows rapid transmission of signals relayed by nerve cells. As a result of genetic mutations, this protective coat is defective in people with CMT1a, slowing the movement of nerve signals from the brain to muscles, and vice versa.

Patients experience gradual muscle weakness and atrophy (shrinkage), as well as decreased sensation, mostly in the feet, lower legs, hands, and forearms.

No approved therapies that the underlying cause of CMT, and validated measures of clinical disability are poorly sensitive to disease progression, hampering the evaluation of potential treatments in clinical trials.

Instead of using electrophysiological tests, which assess electrical impulses sent by nerve cells, researchers aimed to examine nerve tissue alterations in CMT1a patients using an imaging technology called quantitative MRI (qMRI), which appears to be highly sensitive to changes over time.

Using that technology, a team at Aix-Marseille University, France, assessed differences between patients and healthy individuals (control group) across a range of measures, including nerve volume, proton density (which offers information for different structures in a given qMRI section), and magnetization transfer ratio (which assesses how different molecules transfer energy to one another).

These measures were assessed in the thigh (sciatic nerve) and in the leg (tibial nerve), since it is unclear which limb region best correlates with other measures of clinical disability. A gradient of measures from thigh to leg was also examined.

The analysis included 32 CMT1a patients, average age 37.5, and 13 controls matched to patients by age and sex. Patients had CMT for about 25 years, with symptoms appearing in childhood in most of them.

Results showed that nerve volume and proton density were significantly higher in patients than controls in both nerve regions examined. Magnetization transfer ratio, in contrast, was significantly lower in patients in both the sciatic and tibial nerves.

Controls had a nerve volume that increased in the thigh from the more distal region (closer to the leg) to the more proximal region (closer to the hip), results also showed. This thigh gradient was not seen in patients.

But controls had no volume gradient in the leg region, while patients had increases in the volume of their tibial nerve from the proximal to distal region.

Yet, a ratio of measures in the sciatic and tibial nerves was not significantly different between patients and controls. This was true for all three measures of nerve tissue alterations: nerve volume, proton density, and magnetization transfer ratio.