Table 4

Main findings, recommendations and future research directions

Topic	Main findings	Future 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.
Treatment	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.