Finally - a true “function” test

Article Outline

• Copyright

“Functional imaging,” especially of the nervous system, is a particularly exciting advance. Most of this work has been undertaken as part of research protocols, although there are a few ways in which the technology has been making its way into clinical care.

One functional imaging technique which is currently showing both clinical and research promise is positron emission tomography (PET) analysis of the benzodiazepine binding site using ¹¹C flumazenil. This technique indirectly measures GABA_A receptor density and has recently been used in the management of adults with hepatic encephalopathy.

In the current issue of The Journal, Asahina et al in Sapporo Japan have employed this technique to study a genetic disorder involving the GABA_A receptor, Angleman syndrome (AS). Some patients with AS have a large deletion of 15q11-13, which includes some subunits of this receptor. A previous study had suggested that such patients had reduced ¹¹C flumazenil binding by PET. Asahina’s work, however, suggests that the situation is much more complex, in that they demonstrated increased GABA_A available for binding in some of their patients with AS. This work challenges one of the conventional concepts of this disease and has led to the hypothesis that these patients may actually have developmental dysregulation of their receptor expression.

This work is clearly in its early stages, and it is unlikely that this is the final word on the subject. Nonetheless, this fascinating, complicated article provides the reader with a striking example of the utility of functional CNS imaging in a rare disorder.