Against the prevailing assumption, Fabry patients, even those with marked brain structural alterations, showed only mild cognitive deficits. The high frequency of depression in FD is likely to be related to the burden of this chronic multiorganic hereditary disease, but not to the FD-typical brain structural alterations. Longitudinal studies are necessary to clear, if the mild cognitive deficits in FD might precede clinically relevant cognitive decline.

With an accuracy of 87%, basilar artery diameters were superior to all other MR measures for separating patients with Fabry disease (FD) from controls. Future studies should adopt basilar artery measurements for early detection and monitoring of brain involvement in FD. Moreover, further investigations should reveal if the dilated vasculopathy in FD could be a screening marker to detect FD in a cohort of other cerebrovascular diseases, especially in cryptogenic stroke.

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Background: Fabry disease (FD) is a lysosomal storage disorder associated with marked cerebrovascular disease. Conventional MRI shows an extensive load of white matter lesions (WMLs) which may already be present at an early stage in the disease. Objective: Investigator independent and sensitive quantification of structural changes in the brain in clinically affected men and women with FD. Methods: We performed a voxel based analysis of diffusion tensor images (DTI) in 25 patients with FD and 20 age matched normal controls. Results: DTI revealed significant increases in cerebral white matter mean diffusivity (MD) in patients with FD, which were pronounced in the periventricular white matter. Even the subgroup of patients without significant WMLs load (n = 18) showed increased diffusivity in the cerebral white matter. In gray matter areas, MD elevation was detected only in the posterior part of the thalamus, independent of the visible pulvinar alterations on T1 weighted images. Voxel based fractional anisotropy measurements did not differ significantly between patients and controls. Conclusions: The present study demonstrates the clinical feasibility of voxel based analysis of DTI as a sensitive tool to quantify brain tissue alterations in FD. The pattern of increased brain tissue diffusivity is probably due to microangiopathic alterations, mainly affecting the long perforating arteries.

The mechanisms and functional consequences of ischemia-induced injury during perinatal development are poorly understood. Subplate neurons (SPn) play a central role in early cortical development and a pathophysiological impairment of these neurons may have long-term detrimental effects on cortical function. The acute and long-term consequences of combined oxygen and glucose deprivation (OGD) were investigated in SPn and compared with OGD-induced dysfunction of immature layer V pyramidal cortical neurons (PCn) in somatosensory cortical slices from postnatal day (P)0-4 rats. OGD for 50 min followed by a 10-24-h period of normal oxygenation and glucose supply in vitro or in culture led to pronounced caspase-3-dependent apoptotic cell death in all cortical layers. Whole-cell patch-clamp recordings revealed that the majority of SPn and PCn responded to OGD with an initial long-lasting ischemic hyperpolarization accompanied by a decrease in input resistance (R(in)), followed by an ischemic depolarization (ID). Upon reoxygenation and glucose supply, the recovery of the membrane potential and R(in) was followed by a Na+/K+-ATPase-dependent postischemic hyperpolarization, and in almost half of the investigated SPn and PCn by a postischemic depolarization. Whereas neither a moderate (2.5 mm) nor a high (4.8 mm) increase in extracellular magnesium concentration protected the SPn from OGD-induced dysfunction, blockade of NMDA receptors with MK-801 led to a significant delay and decrease of the ID. Our data demonstrate that OGD induces apoptosis and a profound dysfunction in SPn and PCn, and underline the critical role of NMDA receptors in early ischemia-induced neuronal damage.