A recent study suggests emerging evidence of a connection between CMTX1 and Multiple Sclerosis (MS).

A recent study by Georgios Koutis et al at the National and Kapodistrian University of Athens recently in The Journal of Neurology, Neurosurgery and Psychiatry suggested emerging evidence of a connection between CMTX1 and Multiple Sclerosis (MS).

Because this would be concerning to patients who have CMTX1, the clinical team at the CMT Center of Excellence at University College London’s (UCL) Institute of Neurology in London looked into their patient database of 133 patients with CMTX1.

In summary, not one patient at UCL had a clinical diagnosis of MS and CMTX1.   Twenty-six of those patients with CMTX1 had MRIs of the brain for other symptoms, but only one had lesions which could be indicative of MS; he did not have a clinical diagnosis of MS.

There are two points in the study by Koutsis et al  which are noteworthy:

  • Only a very small number of patients with CMTX1 were evaluated by Koutsis et al, and
  • CMTX1 can cause lesions in the white matter of the brain that are unrelated to MS.

Due to the prevalence of MS and CMTX1 in the general population, MS and CMTX1are likely to co-exist in some patients.  Furthermore, because CMTX1 can cause harmless lesions on the brain, MS could be easily misdiagnosed. According to the team at UCL, there is no evidence to suggest that CMTX1 causes MS.

Dr. Alex Rossor, a member of the CMT Research Foundation’s Scientific Advisory Board, is on the clinical team at UCL and is an author of the letter written in response and recently published in the The Journal of Neurology, Neurosurgery and Psychiatry. Dr. Rossor reviewed this statement and approved it for public dissemination.  The formal letter from the team at UCL is below.

We read with interest the study by Koutsis et al. reporting an increased prevalence of multiple sclerosis (MS) in their cohort of patients with X-linked Charcot Marie tooth disease (CMTX1) [1]. CMTX1 is a neurological condition with significant disability. The suggestion that CMTX1 may be a risk factor for developing multiple sclerosis will be of significant concern for these patients.
We have a large cohort of patients with CMTX1 (n=133) in our centre. If the association between multiple sclerosis and CMTX1 were true we would expect to see a similar prevalence of multiple sclerosis to that reported by Koutsis et al., we therefore reviewed the clinical records and brain MRI of all patients with CMTX1.
Patients with confirmed GJB1 mutations were identified from our internal database of individuals with CMT seen at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. The brain MRI scans of all patients with CMTX1 who underwent imaging (n=26) were reviewed. Of the 26 MRI scans performed, 10 were identified as being abnormal and reviewed with a neuroradiologist. This translates to 7.52% of all CMTX1 patients in our cohort.
Of the 10 abnormal scans, only one patient had MRI Brain imaging with T2 white matter lesions (T2WML) resembling those seen in MS – periventricular, and perpendicular to ventricles. This patient at age 61, has accumulated only one new lesion over four years, has not had a clinical attack and as such does not meet criteria for either radiologically isolated syndrome (RIS) or MS [2,3].
Of the other nine abnormal scans in our cohort, five patients were characterised as having nonspecific focal T2 weighted hyperintensities that were not characteristic of MS-like lesions and did not fulfil criteria for RIS [2]. Two patients had nonspecific diffuse T2 weighted white matter changes; one had diffuse splenium and corpus colossum T2 weighted matter changes; and one with isolated volume loss. There was no correlation between the genotype and imaging phenotype.
Four patients had serial imaging which did not demonstrate any new lesions. The clinical indications for performing a brain MRI in our cohort were subtle upper motor neuron signs.
The presence of T2WML in CMTX1 is well described [4]. While these changes appear prevalent in our CMTX1 cohort, no patients had relapsing features or clinical episodes that would fulfil diagnostic criteria for MS. Additionally, diagnostic criteria for RIS require that there is no alternate explanation for the changes seen, and as yet, the spectrum of T2WML in CMTX remains uncharacterised.
Thus, in a larger cohort of patients than that reported by Koutsis et al. we have not identified an increased prevalence of MS in patients with CMTX1 and certainly nothing like the relative risk suggested by Koutsis et al of 23.8. With a population prevalence of 1:1000 [1, 2] MS is likely to co-exist in the CMT population and based on our cohort we do not believe there to be an emerging association between CMTX1 and MS.