OBJECTIVE: Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit 
of the KATP channel, result in permanent neonatal diabetes mellitus. They also 
may cause neurologic symptoms such as mental retardation and motor problems 
(iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is 
reported to alleviate both the neurologic symptoms and diabetes in such cases. 
The study aimed to establish the magnitude and functional basis of the effect of 
SUs on the neurologic phenotype in children with iDEND using neuroimaging before 
and after insulin replacement with glibenclamide.
RESEARCH DESIGN AND METHODS: To localize and quantify the effect of 
glibenclamide administration, we performed single-photon emission computed 
tomography in seven patients with different mutations in KCNJ11. In five 
patients, measurements before and after initiation of SU treatment were 
performed. RESULTS Significant changes in single-photon emission computed 
tomography signal intensity after transfer to SU therapy were restricted to the 
cerebellum, consistent with previous data showing high Kir6.2 expression in this 
brain region. Cerebellar perfusion improved for both left (P = 0.006) and right 
(P = 0.01) hemispheres, with the mean improvement being 26.7 ± 7.1% (n = 5). No 
patients showed deterioration of cerebellar perfusion on SU therapy. 
Electrophysiological studies revealed a good correlation between the magnitude 
of KATP channel dysfunction and the clinical phenotype; mutant channels with the 
greatest reduction in adenosine 5'-triphosphate inhibition were associated with 
the most severe neurologic symptoms.
CONCLUSIONS: We conclude it is likely that at least some of the beneficial 
effects of SU treatment on neurodevelopment in iDEND patients result from 
improved cerebellar perfusion.