Rates of white matter hyperintensities compatible with the radiological profile of multiple sclerosis within self-referred synesthete populations

Abstract

Synesthesia is an inherited condition causing unusual secondary sensations (e.g, sounds might be experienced as both auditory and visual percepts). The condition has been linked with cognitive and perceptual benefits and is considered a benign alternative form of perception. Here, we investigate self-referred synesthete populations and their rates of radiologically determined white matter hyperintensities (WMH) of a type compatible with the McDonald imaging criteria for the diagnosis of multiple sclerosis (MS). MS is a chronic condition resulting in damage to myelination surrounding nerve fibers of the central nervous system (CNS). Magnetic resonance imaging (MRI) features highly suggestive of MS without overt clinical symptoms are termed radiologically isolated syndrome (RIS). We present data showing that the shared MRI profile of MS and RIS has been significantly overrepresented in synesthetes who have participated in neuroimaging research. We present validation of the clinical and MRI status of these synesthetes and an analysis showing the significant probability their unusual numbers may not have arisen by chance. We discuss how to interpret significant data based on small case numbers and consider the implications of our findings for synesthesia’s clinical status.

Keywords:

• synaesthesia
• synesthesia
• multiple sclerosis
• radiologically isolated syndrome
• comorbidity

Acknowledgments

We are grateful to Daisy Mollison for her radiological expertise, to Richard Shillcock for his feedback on the manuscript, to Linda Williams (Centre for Population and Health Sciences) for her epidemiological and statistical guidance, and to Catherine Oppenheim and Lucie Hertz-Pannier for their help retrieving archived data. The authors declare no competing interests.

Notes

1. Where MS-RIS anomalies were found, authorship was invited for the current article and this would explain why three cases were found in our own cohort but not elsewhere.

2. Calculation of the rate of female MS in Europeans: Pugliatti et al. (2006) report that “the total estimated prevalence rate of MS [in Europe] for the past three decades is 83 per 100 000 with … a female: male ratio around 2.0” (p. 700). On this basis, and given the overall population sex ratio in the European Union (0.96 males to each female; The World Factbook, 2011, Washington, DC: Central Intelligence Agency, 2011), we calculate the estimated European female MS rate at 110/100,000.

3. Calculation of the rate of female MS in England: There was no available data for female MS prevalence in England per se and so we calculated this based on the rate of MS in eastern England (153/100,000; the highest regional rate in England reported by Compston et al., 2006) and the male: female ratio of MS (2:1; Compston et al., 2006) in combination with the overall population prevalence of women versus men in the United Kingdom (1.01:1; The World Factbook, 2011, Washington, DC: Central Intelligence Agency, 2011). This gives an estimate of female MS in England at 204/100,000.

4. Analyzing the RIS cases and MS case separately serves an additional purpose. The MS case was the first reported case and as such can be viewed as the observation that led to the forming of our hypothesis. It could be argued that including this case in subsequent analyses, especially given the small numbers of cases involved, may lead to inappropriate conclusions being drawn. It is important to point out therefore that when this initial case is excluded and the subsequent two cases are analyzed, the outcome remains statistically significant, adding further methodological rigor for this hypothesis.

Additional information

Funding

DAC was supported in part by grants [grant number EP/F500385/1], [grant number BB/F529254/1] for the University of Edinburgh, School of Informatics Doctoral Training Centre in Neuroinformatics and Computational Neuroscience (www.anc.ac.uk/dtc) from the UK Engineering and Physical Sciences Research Council (EPSRC), UK Biotechnology and Biological Sciences Research Council (BBSRC), and the UK Medical Research Council (MRC).