Letter re: Alterations of functional connectivity of the motor cortex in Fabry disease: An RS-fMRI study

Cocozza et al.1 confirmed, by use of resting-state (RS)–fMRI, previous clinical and electrophysiologic studies showing involvement of cerebral motor circuits in Fabry disease (FD), independently of cerebrovascular signs/symptoms and brain MRI lesions.1–3 In particular, they showed alterations of functional connectivity in a polysynaptic motor circuit involving motor cortices, basal ganglia, and right cerebellar hemisphere.1 In metabolic/lysosomal storage diseases, a subclinical CNS impairment is common and may be related, regardless of brain MRI findings, either to a structural irreversible or to a biochemical reversible brain lesion.4,5 A crucial unsettled question in the article is the usefulness of RS-fMRI in detecting subtle and potentially reversible biochemical brain lesions in patients with FD at a rather early appearance. We investigated this question in a previous study by analyzing the effect of 1 year of enzyme replacement therapy (ERT) on cortical excitability in 5 patients with FD without brain MRI lesions, and an increase of excitatory neurotransmission in motor cortex circuits, documented by transcranial magnetic stimulation (TMS).3 We observed a reduction in motor cortex hyperexcitability in all patients after ERT, indicating the possible utility of TMS, and likely of other techniques such as RS-fMRI, in monitoring the disease course and the response to therapy.