Primary motor cortex hyperexcitability in Fabry’s disease

ObjectiveInvolvement of pyramidal cells and/or changes in excitability of brain areas remote from an ischemic stroke has been demonstrated. Since in Fabry disease (FD), specific cerebrovascular lesions are present, we thought to investigate motor cortex excitability, using transcranial magnetic stimulation.MethodsResting (RMT) and active (AMT) motor threshold, input–output curve (IN–OUT), central motor conduction time (CMCT), cortical silent period (cSP), short and long interval intracortical inhibition (SICI and LICI), intracortical facilitation (ICF), short interval intracortical facilitation (SICF) and short afferent inhibition (SAI) were measured in the cortical representation of the right first dorsal interosseous muscle in 11 patients with FD and 11 sex- and age matched healthy subjects.ResultsFD patients showed a significant increase of steepness in IN–OUT, ICF and SICF curves. RMT, AMT, CMCT, SICI, LICI and SAI were normal.ConclusionsOur data documented an increased activity of motor cortex glutamatergic excitatory circuits in FD, evident also in patients without brain MRI lesions. Following enzyme replacement treatment, this abnormality was partly reversed.SignificanceWe suggest that our findings are expression of subtle “biochemical brain lesions”, due to an early involvement of neurons and/or astrocytes by the cascade of pathologic events leading to brain damage in FD.

► Primary motor cortex excitability was evaluated in patients with Fabry disease using transcranial magnetic stimulation. ► Results demonstrated an increased activity of motor cortex excitatory circuits that was also present in patients without conventional MRI brain lesions. ► Following one year of treatment with enzyme replacement therapy, this abnormal excitability was partly reversed.