Fabry and the brain: Incorporating patients’ illness perceptions into the physicians’ practice

Cerebral involvement is common in Fabry disease (FD). This thesis aimed to incorporate patients’ illness perception (e.g. depressive symptoms, quality of life) into the physicians’ practice (follow-up schedules and treatment). We aimed to improve prognostication, prevent cerebral involvement and stimulate appropriate use of enzyme replacement therapy (ERT). In the Dutch FD cohort, cognitive impairment, subjective cognitive complaints and depressive symptoms were all found, with a high prevalence of the latter two. Assessment of depressive symptoms using a questionnaire should be included in routine follow-up of FD patients. Progression of white matter lesions (WMLs) and infarctions was related to the patients’ age, sex and phenotype. Unexpectedly, we found no association between progression of WMLs or infarctions and ERT or cerebrovascular risk factors. This provided a sobering view of the manageability of WMLs and infarctions in FD. Patients should be informed that WMLs will increase with age, despite treatment with ERT. FD patients with a history of stroke experienced a decreased quality of life and had a higher risk of cognitive impairment, emphasizing the importance of preventing stroke. WMLs were not related to cognitive functioning or depressive symptoms, showing there is a need for clinically relevant and validated cerebral biomarkers. In conclusion, we believe that this thesis may improve communication between doctors and patient, guides the appropriate use of ERT and gives clear directions for future research. We also make a plea for longitudinal studies for FD, with smart designs and robust methodology to improve comparability and interpretability of results