Is There Room for MR Imaging in the Assessment of Hereditary Motor and Sensory Neuropathies?

Hereditary motor and sensory neuropathies (HMSN) are a group of neurologic diseases, which are highly heterogeneous in terms of both their genetic background and their pathologic and clinical manifestations. In the past 3 decades, considerable advances in the understanding of this group of disorders have been made, which formed the basis for their classification and diagnosis. At present, diagnosis of HMSN is based on information derived from its mode of inheritance and clinical course, as well as from neuropathological, neurophysiological, and molecular genetic findings.

In the past few years, based on the concept that MR imaging is a noninvasive way to look at nervous system pathology, a question has been raised as to whether there is any room for MR imaging in the assessment of HMSN. Several preliminary case reports showed that MR imaging has the potential to detect enlarged nerve roots in those types of HMSN that are known to determine hypertrophic nerve changes. Nerve root enlargement on MR images is, however, a disease-nonspecific sign, and, as a consequence, the detection of nerve root enlargement on MR images does not modify the “classical” approach to diagnosis and classification of HMSN. It is not surprising, therefore, that when reading through the MR literature on HMSN the primary conclusion is that the role of MR imaging in the assessment of these disorders can only be marginal, and that these studies are driven more by the increased availability of MR scanners rather than by a clinical need or a genuine research interest.

One of the major merits of the article by Cellerini et al published in this issue of the AJNR (page 1793) is to mitigate this negative feeling. This study provides a systematic MR evaluation of the cauda equina and intradural nerve root abnormalities from a series of 10 patients with type I, II, and III HMSN. It also presents correlations between MR imaging and histopathological findings from sural nerve biopsy. The study confirms that MR imaging has the potential to detect enlarged nerve roots in patients with type I HMSN, in the absence of palpable peripheral nerve enlargement. This change was found to be associated with the presence of onion bulbs in the sural nerves. Most important, however, is that nerve root enlargement was observed in two patients with atypical clinical manifestations (consisting of progressive urinary bladder dysfunction and severe low back pain), suggesting a clinically meaningful role for MR imaging in the diagnosis of, at least, some cases of type I HMSN. Although interesting, the value of this observation in clinical practice is questionable. Diagnostic MR imaging is, in fact, usually obtained in the context of undiagnosed clinical conditions, and one might argue whether subtle changes of nerve root size, potentially useful to suggest a diagnosis of type I HMSN, would be detected in patients with no clinical suspicion of having such a disorder.

This study also shows that diffuse enhancement of intradural nerve roots is a relatively frequent finding in patients with type I and III HMSN. Because no inflammatory changes of the sural nerves from these patients were seen histopathologically, nerve root enhancement in these conditions is likely to be secondary to blood-nerve barrier increased permeability, which in turn may be the result of either blood-nerve barrier congenital defects or ongoing demyelination. Interestingly, enhancement was not seen in the two patients with type II HMSN. If confirmed by larger patient series, this is another potentially relevant finding of the study by Cellerini et al. Although genetic, neuropathological, and neurophysiological findings are different in patients with type I and type II HMSN, they are, in fact, virtually undistinguishable in terms of clinical findings and course. Therefore, it is tempting to speculate that nerve root enhancement in the context of HMSN might be helpful in distinguishing patients with type I HMSN from those with type II HMSN. Given the relatively benign course of the two conditions and the absence of any treatment option, one might, however, argue that this differentiation is no more than an academic exercise.

In clinical neurology, MR imaging is not simply a powerful diagnostic tool, but it is also an intriguing way to understand in vivo the mechanisms of a disease's manifestations and evolutions. To establish this role, however, there is a large amount of work to be done in order to link firmly MR imaging findings with histopathologic changes. Therefore, apart from the above-mentioned specific merits, the paper by Cellerini et al has another more general merit, which goes beyond the actual results of the study. The authors have shown that, although challenging (especially in CNS disorders), correlating MR imaging and histopathologic analysis might be a rewarding exercise in increasing our understanding of the pathophysiological processes of many neurologic conditions.

The study by Cellerini et al, albeit larger than previous studies on the topic, is still based on a relatively small numbers of patients. Nevertheless, the MR imaging findings reported have the potential to be clinically useful in directing physicians toward a diagnosis of type I HMSN in some atypical cases. This calls for a multicenter effort in order to collect data from larger patient samples, with the ultimate goal being able to establish the role of MR imaging in the study of HMSN rigorously. This effort would reduce the number of unnecessary MR imaging examinations as well as facilitate the diagnostic workup in some cases, such as those described by Cellerini et al. At present, the balance between these two conflicting aspects cannot be defined exactly; however, it is likely that the role of MR imaging in the assessment of patients with HMSN will remain modest.