Table 4

Main findings, recommendations and future research directions

TopicMain findingsFuture research directions and recommendations
Age, sex and phenotype
  • Are strongly related to progression of WMLs and infarctions on MRI

  • Should be corrected for in any analysis of variables relating to WMLs or infarctions and evaluating treatment effects in FD.

  • Women with non-classical FD should be compared with the general population to confirm the low rate of FD-related cerebral involvement in this patient group.

  • Patients and doctors should expect progression of WMLs over time, independent of treatment status

  • The effect of very early ERT initiation, before any visual cerebral involvement is present, should be evaluated in high-risk patients (men with classical disease)

  • Older men with classical FD have a high risk of infarction progression, independent of treatment status

  • Presence of some punctate WMLs in patients aged >50 years is not necessarily FD related and treatment initiation should not be solely based on this finding.

  • Randomised controlled trials for new treatment modalities in FD should include MRIs of the brain.

WML assessment
  • Semi-quantitative scales are able to detect WML progression in patients with FD in a long-term follow-up setting

  • White matter lesion volume is preferable to semi-quantitative scales as they provide more detailed information on a continuous scale.

Biomarkers, variables of interest and pathology
  • Changes in BAD, eGFR and LMVi are not related to WML and infarction progression after correction for age, sex and phenotype

  • WMLs and infarctions on MRI are probably end-stage pathological processes. Earlier biomarkers should be explored using sophisticated imaging techniques.

  • The effect of differences in enzyme activity levels and genetic modifiers on progression of WMLs and infarctions should be explored within men with classical disease since interpatient variability is high.

  • Potentially important variables should be assessed prospectively and with advanced methodology (eg, volumetric atrial measurements instead of presence/absence of atrial fibrillation).

  • BAD, basilar artery diameter; eGFR, estimated glomerular filtration index; ERT, enzyme replacement therapy; FD, Fabry disease; LVMi, left ventricular mass index; WML, white matter lesion.