The expanding clinical spectrum of Anderson-Fabry disease: a challenge to diagnosis in the novel era of enzyme replacement therapy

Anderson-Fabry disease is an X-linked recessive lysosomal storage disease resulting from deficient alpha-galactosidase A activity. The conception of the disease has changed within the last decade. Studies of the last years have shown that the disease is not limited to the classical full-blown manifestation in affected males, which is well known since more than a century, but may also occur in carrier females. The phenomenology may differ in severity and kind of organ manifestation. Cardiac and renal variants with solely disease manifestation of these organs have also been described in an increasing number. It is likely that a spectrum exists regarding alpha-galactosidase A activity in both genders on the one hand, and an additional one regarding the severity and the number of organs affected on the other. The purpose of this review is to sharpen physicians' perception of this disease. Early and accurate diagnosis is mandatory considering that this disorder is now, after introduction of the novel enzyme replacement therapy, a treatable disease.     

Molecular characterization of antibody specificities against myelin/oligodendrocyte glycoprotein in autoimmune demyelination

Myelin/oligodendrocyte glycoprotein (MOG) is a target antigen for myelin-destructive Abs in autoimmune central nervous system demyelinating disorders. Little is known about the molecular and structural basis of these pathogenic Ab responses. Here, we have characterized anti-MOG Ab specificities in the marmoset model of experimental allergic encephalomyelitis, by means of a combinatorial IgG-Fab library. We found that a diverse population of Ig genes encodes for auto-Abs that exclusively recognize conformation-dependent antigenic targets on MOG. These antigenic domains correspond to exposed epitopes in vivo, as the Fab fragments recognize native MOG in situ in marmoset brain tissue. The Ab fragments described here represent Ab specificities that are common constituents of the humoral immune repertoire against MOG in outbred populations, as demonstrated by their ability to displace native anti-MOG Abs present in sera from MOG-immune marmosets and patients with multiple sclerosis. Furthermore, neuropathological analysis and characterization of Ab epitope specificities in animals immunized with MOG or MOG-derived peptides revealed that only conformation-dependent Abs are associated with demyelinating activity, suggesting that epitope recognition is an important factor for Ab pathogenicity. Our findings provide novel and unexpected knowledge on the diversity of anti-MOG Ab responses in nonhuman primates and humans, and will permit the dissection of pathogenic auto-Ab properties in multiple sclerosis.     

Learning curve of medical students in ultrasound-guided simulated nerve block

Background

Good hand-eye coordination is a prerequisite for safe ultrasound-guided peripheral nerve blocks. However, new skills have to be acquired when compared to the traditional nerve stimulation technique. We tested and mathematically described the learning curve of these skills in inexperienced ultrasound users employing a simple phantom of a peripheral nerve.

Methods

A simple phantom made from a piece of spaghetti to simulate a nerve, within a starch core and embedded in gelatine was used for ultrasound-guided simulation of a peripheral nerve block. Eighteen medical students who were novices to ultrasound were enrolled. Serial time to successful injection was measured. Quality of injection was rated by two independent observers.

Results

Time to successful injection improved from a median of 66.5 s (49.5–90) for the first trial to 37 s (23.5–53.5) for the 11th trial. A plateau of 30 s was reached for t _1/2 after 2.7 trials and 4 × t _1/2 after 7.8 trials when described as first-order exponential decay. Time to successful injection was significantly shortened after 5 trials. Quality of injection with numbers of trials followed a sigmoidal shape with 50 % of maximum quality after 3.6 trials and a plateau after 8.5 trials. Likewise, a significant improved quality of injection was reached after 5 trials.

Conclusion

Based on our mathematical analyses of the learning curve, inexperienced ultrasound users can improve their hand-eye coordination within 5 subsequent trials in a simple model of a peripheral nerve block.